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1
Oh, Julyun, and Lorraine Symington. "Role of the Mre11 Complex in Preserving Genome Integrity." Genes 9, no. 12 (2018): 589. http://dx.doi.org/10.3390/genes9120589.
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DNA double-strand breaks (DSBs) are hazardous lesions that threaten genome integrity and cell survival. The DNA damage response (DDR) safeguards the genome by sensing DSBs, halting cell cycle progression and promoting repair through either non-homologous end joining (NHEJ) or homologous recombination (HR). The Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex is central to the DDR through its structural, enzymatic, and signaling roles. The complex tethers DNA ends, activates the Tel1/ATM kinase, resolves protein-bound or hairpin-capped DNA ends, and maintains telomere homeostasis. In addition to its role at DSBs, MRX/N associates with unperturbed replication forks, as well as stalled replication forks, to ensure complete DNA synthesis and to prevent chromosome rearrangements. Here, we summarize the significant progress made in characterizing the MRX/N complex and its various activities in chromosome metabolism.
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Chen, Huan, Roberto A. Donnianni, Naofumi Handa, et al. "Sae2 promotes DNA damage resistance by removing the Mre11–Rad50–Xrs2 complex from DNA and attenuating Rad53 signaling." Proceedings of the National Academy of Sciences 112, no. 15 (2015): E1880—E1887. http://dx.doi.org/10.1073/pnas.1503331112.
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The Mre11–Rad50–Xrs2/NBS1 (MRX/N) nuclease/ATPase complex plays structural and catalytic roles in the repair of DNA double-strand breaks (DSBs) and is the DNA damage sensor for Tel1/ATM kinase activation. Saccharomyces cerevisiae Sae2 can function with MRX to initiate 5′-3′ end resection and also plays an important role in attenuation of DNA damage signaling. Here we describe a class of mre11 alleles that suppresses the DNA damage sensitivity of sae2Δ cells by accelerating turnover of Mre11 at DNA ends, shutting off the DNA damage checkpoint and allowing cell cycle progression. The mre11 alleles do not suppress the end resection or hairpin-opening defects of the sae2Δ mutant, indicating that these functions of Sae2 are not responsible for DNA damage resistance. The purified MP110LRX complex shows reduced binding to single- and double-stranded DNA in vitro relative to wild-type MRX, consistent with the increased turnover of Mre11 from damaged sites in vivo. Furthermore, overproduction of Mre11 causes DNA damage sensitivity only in the absence of Sae2. Together, these data suggest that it is the failure to remove Mre11 from DNA ends and attenuate Rad53 kinase signaling that causes hypersensitivity of sae2Δ cells to clastogens.
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Baraldi, Daniele, Stefan Holmström, Karl-Fredrik Nilsson, Matthias Bruchhausen, and Igor Simonovski. "316L(N) Creep Modeling with Phenomenological Approach and Artificial Intelligence Based Methods." Metals 11, no. 5 (2021): 698. http://dx.doi.org/10.3390/met11050698.
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A model that describes creep behavior is essential in the design or life assessment of components and systems that operate at high temperatures. Using the RCC-MRx data and the LCSP (logistic creep strain prediction) model, processed design data were generated over the whole creep regime of 316L(N) steel—i.e., primary, secondary, and tertiary creep. The processed design data were used to develop three models with different approaches for the creep rate: a phenomenological approach; an artificial neural network; and an artificial intelligence method based on symbolic regression and genetic programming. It was shown that all three models are capable of describing the true creep rate as a function of true creep strain and true stress over a wide range of engineering stresses and temperatures without the need of additional micro-structural information. Furthermore, the results of finite element simulations reproduce the trends of experimental data from the literature.
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Minson, Katherine A., Catherine C. Smith, Alisa B. Lee-Sherick, et al. "MRX2843, a Novel Dual MerTK-FLT3 Inhibitor with Activity Against Resistance-Conferring FLT3 Mutations in Acute Myeloid Leukemia." Blood 124, no. 21 (2014): 3757. http://dx.doi.org/10.1182/blood.v124.21.3757.3757.
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Abstract Internal tandem duplication mutations of the FLT3 tyrosine kinase (FLT3-ITDs) are present in 15-30% of cases of pediatric and adult acute myeloid leukemias (AML), and are known to portend a poor prognosis. Over the past decade small molecule inhibitors targeting FLT3 have entered clinical trials. Although initial responses have been observed, patients typically develop resistance to current FLT3 inhibitors during the first year of therapy via acquisition of or selection for point mutations in the FLT3 kinase domain at amino acid F691 or D835. Although FLT3 is the most commonly targeted protein in AML, other candidates for pharmacologic inhibition have been identified. Ectopic expression of MerTK, a receptor tyrosine kinase, has been identified in 80-100% of primary AML patient samples, and previous data demonstrate anti-leukemic effects in response to shRNA-mediated MerTK inhibition. Here we describe MRX2843, a novel small molecule inhibitor of MerTK and FLT3 with activity against FLT3 point mutations and therapeutic efficacy in mouse xenograft models of AC220-resistant AML. MRX2843 potently inhibits MerTK and FLT3 with enzymatic IC50 values of 1.3 and 0.64nM, respectively. Treatment of two AML cell lines that express a FLT3-ITD mutation (MV4;11 has low MerTK expression; MOLM-14 does not express MerTK), and two AML cell lines that express MerTK but do not have activating mutations in FLT3 (U937, Kasumi-1) with 25-300nM MRX2843 abrogated activation of intracellular signaling pathways downstream of FLT3 and MerTK, including AKT and ERK1/2. In addition, 72 hour treatment with MRX2843 led to induction of apoptosis in AML cell lines compared to vehicle-treated controls, as determined by flow cytometic analysis after staining with YO-PRO-1 iodide and propidium iodide. For example, in MOLM-14 cultures, treatment with MRX2843 resulted induction of apoptosis in 84±2% of cells, compared to 5±2% after vehicle treatment (p<0.001). In soft agar or methylcellulose cultures, treatment of AML cell lines and patient samples with MRX2843 resulted in an 80-90% reduction in colony number. To determine the effects of MRX2843 treatment in vivo, a patient-derived murine xenograft model was established by intravenous injection of primary AML patient blasts that express both MerTK and FLT3-ITD into NOD-SCID-gamma (NSG) mice. Engraftment was monitored by flow cytometric determination of peripheral blast count. When ~10% peripheral blasts were detected, mice were randomized to treatment with 50mg/kg MRX2843 or vehicle (saline) once daily by oral gavage. Treatment with MRX2843 significantly prolonged survival (median survival of 96 days after MRX2843 treatment versus 16 days in control mice, n=4 per group, p<0.01). Two derivatives of the human FLT3-ITD AML cell line MOLM-14, which acquired either the D835Y (activation loop) or F691L (gatekeeper) mutation after selection in escalating doses of the FLT3 inhibitor AC220, were used to test the activity of MRX2843 against clinically relevant FLT3 point mutations. Treatment with MRX2843 resulted in a significant reduction in the number of viable cells after 48 hours of culture in MOLM-14, MOLM-14:D834Y, and MOLM-14:F691L with IC50 values of 17nM, 20nM, and 30nM, respectively. In both mutant cell lines, MRX2843 potently inhibited phosphorylation of FLT3 and abrogated activation of downstream intracellular signaling molecules. Treatment with MRX2843 induced cell death in MOLM-14:D835Y (80±7% versus 10±1%, p<0.001) and in MOLM14:F691L (61±16% versus 12±1%, p<0.001). In contrast, both cell lines were resistant to treatment with AC220 at concentrations 20-fold higher than the inhibitory concentration in the parental line. A murine model of AC220-resistant AML was developed by intravenous injection of MOLM-14:D835Y cells into NSG mice. Daily treatment with saline, 10mg/kg AC220, or 50mg/kg MRX2843 was administered by oral gavage beginning 4 days after transplant. Treatment with MRX2843 significantly prolonged survival when compared to mice treated with saline or AC220 with median survival of 103 days, 33 days, and 48 days, respectively (n=5 per group, p<0.01, Figure 1). In summary, MRX2843 is a novel MerTK and FLT3 inhibitor that retains activity against clinically relevant, resistance-conferring FLT3 point mutations and prolongs survival in murine models of AML. These data support further development of MRX2843 and advancement to early phase clinical trials. Disclosures DeRyckere: University of Colorado - Denver: targeting of the Mer tyrosine kinase as cancer therapy Patents & Royalties; Meryx, Inc: Equity Ownership. Wang:University of North Carolina Chapel Hill: MRX-2843 Patents & Royalties; Meryx, Inc: Equity Ownership. Frye:University of North Carolina Chapel Hill: MRX-2843 Patents & Royalties; Meryx, Inc: Equity Ownership. Earp:University of North Carolina Chapel Hill: MRX-2843 Patents & Royalties; University of North Carolina Chapel Hill: targeting of the Mer tyrosine kinase as cancer therapy Patents & Royalties; Meryx, Inc: Equity Ownership. Graham:University of Colorado - Denver: MRX-2843 Patents & Royalties; University of Colorado - Denver: targeting of the Mer tyrosine kinase as cancer therapy Patents & Royalties; Meryx, Inc: Equity Ownership.
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Rouillard, Fabien, Brigitte Duprey, Jean-Louis Courouau, et al. "Evaluation of cobalt free coatings as hardfacing material candidates in sodium-cooled fast reactor and effect of oxygen in sodium on the tribological behaviour." EPJ Nuclear Sciences & Technologies 5 (2019): 10. http://dx.doi.org/10.1051/epjn/2019025.
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The feedback produced by operating Sodium-cooled Fast Reactors (SFRs) has shown the importance of material tribological properties. Where galling or adhesive wear cannot be allowed, hardfacing alloys, known to be galling-resistant coatings, are usually applied on rubbing surfaces. The most used coating is the cobalt-base alloy named Stellite 6® because of its outstanding friction and wear behaviour. Nevertheless, cobalt is an element which activates in the reactor leading to complex management of safety during reactor maintenance and mainly decommissioning. As a consequence, a collaborative work between CEA, EDF and FRAMATOME has been launched for selecting promising cobalt-free hardfacing alloys for the 600 MWe Sodium-cooled Fast breeder reactor project named ASTRID. Several nickel-base alloys have been selected from literature review then deposited by Plasma Transferred Arc or Laser Cladding on 17Cr austenitic stainless steel 316L(N) according to RCC-MRx Code (AFCEN Code). Among the numerous properties required for qualifying their use as hardfacing alloys in SFR, good corrosion behaviour and good friction and wear behaviour in sodium are essential. First results on these properties are shown in this article. Firstly, the corrosion behaviour of all coatings was evaluated through exposure tests in purified sodium for 5000 h at 400 °C. All coatings showed an acceptable corrosion behaviour in sodium. Finally, the friction and wear properties of one alloy candidate, NiCrBSi alloy, were studied in sodium in a dedicated designed facility. The influence of the oxygen concentration in sodium on the friction and wear properties was evaluated.
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Díaz, Juan, Lucero Salgado, and Rafael Roeder. "Sobrevida con mastectomía radical en cáncer de mama invasor." Revista Peruana de Ginecología y Obstetricia 45, no. 2 (2015): 97–105. http://dx.doi.org/10.31403/rpgo.v45i1373.
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OBJETIVOS: Comparar las tasas de sobrevida a largo plazo según diversos factores clínico-patológicos y terapéuticos y determinar las tasas de sobrevida y recurrencia decenal luego de mastectomía radical clásica (MRC) y mastectomía radical modificada (MRM). MATERIAL Y MÉTODOS: Revisamos retrospectivamente las historias clínicas de 72 pacientes con carcinoma de mama invasor operable con axila negativa (n=38) o positiva (n=34), tratadas con MRC(n=57) o MRM (n=15) en el Hospital Belén, Trujillo, Perú, desde el 1° de enero de 1966 al 31 de diciembre de 1995. RESULTADOS: La edad media fue 47,6 ± 9,5 años (límites, 30 a 70 años). El tiempo medio de enfermedad fue 9 meses (límites, 0,3 a 156 meses). Los síntomas o signos más frecuentes fueron presencia del tumor (100%) y dolor mamario (37,5%). Las tasas de sobrevida decenal en las pacientes tratadas con MRC y MRM, según el método actuarial de Kaplan-Meier, fueron 58% y 54%, respectivamente (p=NS). No hubo diferencia significativa en la tasa de sobrevida decenal entre el grupo de MRC y MRM al considerar el tamaño tumoral, número de ganglios regionales positivos, nivel axilar comprometido, estadio patológico y tipo de tratamiento. En las pacientes con ganglios axilares negativos hubo una mejora significativa en la sobrevida decenal cuando fueron tratadas con MRC que con MRM (68% contra 38%, p < 0,05). Las tasas decenales de recurrencia local, regional y a distancia en el grupo de MRC, fueron 21 %, 1,8% y 24,6%, respectivamente, mientras que el grupo de MRM las tasas decenales de recurrencia local, regional y a distancia fueron 13,3% 10% y 26, 7%, respectivamente (p=NS). CONCLUSIONES: En pacientes con carcinoma de mama operable, la sobrevida decenal es similar cuando éstas son tratadas con MRC y MRM; sin embargo en las pacientes con ganglios axilares negativos, la sobrevida decenal es influida favorablemente por la MRC.
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Holmström, Stefan, Frits De Haan, Ulrich Führer, Rami Pohja, and Jaromir Janousek. "Engineering models for softening and relaxation of Gr. 91 steel in creep-fatigue conditions." International Journal of Structural Integrity 8, no. 6 (2017): 670–82. http://dx.doi.org/10.1108/ijsi-02-2017-0010.
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Purpose There are a number of different approaches for calculating creep-fatigue (CF) damage for design, such as the French nuclear code RCC-MRx, the American ASME III NH and the British R5 assessment code. To acquire estimates for the CF damage, that are not overly conservative, both the cyclic material softening/hardening and the potential changes in relaxation behavior have to be considered. The data presented here and models are an initial glimpse of the ongoing European FP7 project MATISSE effort to model the softening and relaxation behavior of Grade 91 steel under CF loading. The resulting models are used for calculating the relaxed stress at arbitrary location in the material cyclic softening curve. The initial test results show that softening of the material is not always detrimental. The initial model development and the pre-assessment of the MATISSE data show that the relaxed stress can be robustly predicted with hold time, strain range and the cyclic life fraction as the main input parameters. The paper aims to discuss these issues. Design/methodology/approach Engineering models have been developed for predicting cyclic softening and relaxation for Gr. 91 steel at 550 and 600°C. Findings A simple engineering model can adequately predict the low cycle fatigue (LCF) and CF softening rates of Gr. 91 steel. Also a simple relaxation model was successfully defined for predicting relaxed stress of both virgin and cyclically softened material. Research limitations/implications The data are not yet complete and the models will be updated when the complete set of data in the MATISSE project is available. Practical implications The models described can be used for predicting P91 material softening in an arbitrary location (n/Nf0) of the LCF and CF cyclic life. Also the relaxed stress in the softened material can be estimated. Originality/value The models are simple in nature but are able to estimate both material softening and relaxation in arbitrary location of the softening curve. This is the first time the Wilshire methodology has been applied on cyclic relaxation data.
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Franke, Georg-Nikolaus, Jacqueline Maier, Kathrin Wildenberger, et al. "Quantification of BCR-ABL with Digital PCR Results in a Significantly Lower Rate of Deep Molecular Responses When Compared to RT-qPCR in CML Patients Treated in the ENEST1st Trial." Blood 126, no. 23 (2015): 135. http://dx.doi.org/10.1182/blood.v126.23.135.135.
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Abstract Digital PCR (dPCR) generates an absolute read out that is largely tolerant to variations in PCR efficiency, reducing the requirement for standardisation like the conversion of the BCR-ABL/ABL ratio to international scale (IS). The aim of this study was to compare the results of dPCR to qPCR in blinded samples from two independent laboratories with respect to the observed rates of molecular response (MR) in CML patients (pts) having undergone 18 months of nilotinib treatment in the ENEST1st trial. A total of 230 cDNA samples from CML pts treated within the ENEST1st trial with e13 or e14/a2 BCR-ABL fusion genes were analysed in Leipzig (L, n=75) or Mannheim (M, n=155) with qPCR between 2012 and 2013. BCR-ABL levels were determined relative to those of ABL and standardization was achieved using plasmid DNA. Both labs are accredited by the European Treatment Outcome Study (EUTOS) collaboration. The cDNA samples were blinded for the qPCR results and re-analysed in L with a duplex dPCR using a QX200 Droplet Digital PCR System (BIO-RAD). In line with the manufacturer's recommendations, samples yielding a minimum of 3 positive droplets in duplicates from the 12-19.000 routinely analysed were scored as positive (+). Depth of MR was scored using the EUTOS definitions used in the ENEST1st trial. For the whole cohort, the median copy number (CN) of BCR-ABL and ABL was 12 and 59350 by dPCR and 10 and 53537 by qPCR, respectively. Both methods detected similar numbers of BCR- ABL+ samples (dPCR 186, qPCR 189) with a median % BCR-ABL 0.022 by dPCR compared 0.013 by qPCR after conversion to IS. 90% of the BCR-ABL+ samples with dPCR were within an deviation of 4.06 -fold (median 1.22 fold) from qPCR for BCR-ABL, 1.77 fold (median 1.06 fold) for ABL and 6.43 fold (median 1.72 fold) for %BCR-ABLIS. Samples from L showed median CN with dPCR and qPCR for BCR-ABL (9 and 10) and ABL (29670 and 30734) with a correlation R2 = 0.95 and 0.84. The median % BCR-ABL was 0.02% by dPCR and 0.03% before and 0.01% after conversion to IS with qPCR. 90% of the BCR-ABL+ samples by dPCR were within a range of 2.9 -fold deviation (median 0.66 fold) from qPCR for BCR-ABL, 1.9 fold (median 0.91 fold) for ABL, 2.6 fold (median 0.74 fold) for %BCR-ABL and 7.5 fold (median 1.96 fold) for %BCR-ABLIS. Samples from M had higher median CN for BCR-ABL and ABL (16 and 80000) by dPCR compared to qPCR (10 and 66570). Correlation was better for BCR-ABL compared to ABL with R2=0.95 and R2 = 0.74. The median % BCR-ABL was 0.022 by dPCR compared to 0.017 and 0.015 with qPCR after conversion to IS. 90% of the BCR-ABL positive samples with dPCR were within a deviation of 4.7 -fold (median 1.6 fold) from qPCR for BCR-ABL, 1.7 fold (median 1.1 fold) for ABL, 4.9 fold (median 1.5 fold) for %BCR-ABL and 5.6 fold (median 1.4 fold) for %BCR-ABLIS. The cumulative rates of MR3, MR4 and MR4.5 or better @ 18 months of treatment in the ENEST1st trial were 83, 43 and 29% with qPCR. The distribution in MR classes was significantly different between dPCR and qPCR (p<0.001). MR scoring by dPCR resulted in decreased cumulative rates of MR3 (-6%), MR4 (-10%) and MR4.5 or better (-11%). Significantly fewer pts achieved >=MR4 when analysed by dPCR compared to qPCR (n=77 vs. 100, p<0.05). Of the 91, 33, 44 and 23 samples scored MR3, MR4, MR4.5 or MR5 with qPCR, 71 (37%) were one (n=49), two (n=21) or three (n=1) MR classes higher with dPCR. In contrast, only 13% were scored one (n=20) or more (n=5) MR classes deeper, most likely as a result of the cut-off of 3 positive droplets. 51% of the samples were concordant (Table 1). Comparison of samples for which MR was deeper by dPCR against those for which MR was worse by dPCR than by qPCR showed no difference in ABL levels (p=0.6). Conclusions: dPCR tends to read out higher levels of BCR-ABL/ABL than standard qPCR, resulting in the placement of pts in worse MR classes. This effect does not appear to be associated with the amount or quality of material and was observed in two independent pt cohorts. Therefore, dPCR should not be used without careful evaluation and comparison to RT-qPCR. Table 1. Depth of MR according to method of quantification and lab dPCR (n) qPCR >MR3 (M/L) MR3 (M/L) MR4 (M/L) MR4.5 (M/L) MR5 (M/L) n (M/L) >MR3 37 (26/11) 1 (0/1) 1 (1/0) 0 0 39 (27/12) MR3 16 (7/9) 68 (48/20) 6 (4/2) 0 1 (1/0) 91 (60/31) qPCR (n) MR4 0 15 (10/5) 10 (6/4) 5 (3/2) 3 (3/0) 33 (22/11) MR4.5 0 15 (7/8) 12 (7/5) 9 (4/5) 8 (7/1) 44 (25/19) MR5 0 1 (1/0) 6 (5/1) 6 (6/0) 10 (9/1) 23 (21/2) dPCR n (M/L) 53 (33/20) 100 (66/34) 35 (23/12) 20 (13/7) 22 (20/2) 230 Disclosures Franke: Novartis: Other: Travel Costs; BMS: Honoraria; MSD: Other: Travel Costs. Frank:Novartis: Employment. Giles:Novartis: Consultancy, Honoraria, Research Funding. Hochhaus:ARIAD: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Müller:Novartis: Honoraria, Other: CONSULTING OR ADVISORY ROLE, Research Funding; BMS: Honoraria, Other: Consulting or Advisory Role, Research Funding; ARIAD Pharmaceuticals Inc.: Honoraria, Other: Consulting & Advisory Role, Research Funding. Niederwieser:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lange:Novartis: Research Funding.
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Medyanik, Olga V. "The effect of financial anxiety on the insurance behavior of Russians in the context of the 2019-nCoV Pandemic." Vestnik of Saint Petersburg University. Sociology 13, no. 4 (2020): 354–73. http://dx.doi.org/10.21638/spbu12.2020.401.
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In the context of the economic and political uncertainty associated with the 2019-nCoV pandemic, it is necessary to determine the socio-psychological factors involved in the transformation of the behavior of insurance consumers under the influence of a biogenic threat. This study measures financial anxiety and its impact on the insurance behavior of Russian citizens. The correlation, comparative, and regression analyses of the financial anxiety of Russian citizens cover three stages of observation: before the start of the 2019 nCoV pandemic (“FA up to 19 nCoV; N = 766), during the period of quarantine measures announced in Russia in March 2020 (“FA 19-nCoV-1”; N = 856), and after the relaxation of quarantine measures at the end of April 2020 (“FA 19-nCoV-2”; N = 963). Psychological analysis data were obtained from the online survey “Financial anxiety (in the context of insurance)”. The questionnaire is psychometrically reliable and easy to use. It includes five measurement scales: MR1 — Physical manifestations of financial incentive anxiety, MR2 — With money shortages and financial uncertainty, MR3 — The value of insurance coverage, MP4 — Financial Confidence, and MR5 — Perception of insurance and investment risks. It was found that Russian citizens consider it important to have insurance coverage for a “rainy day”, and they showed confidence in the insurance market during the biogenic crisis. However, unfortunately, during the 19-nCoV-1 and 19-nCoV-2 periods, Russian citizens did not feel financially secure, unlike in the period before 19-nCoV. Women showed high scores for physical manifestations of financial anxiety and low financial confidence in the future, in contrast to men, regardless of the observation period.
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Sahin, Ozlem, Murat Cansever, Ender Sirakaya, Nicola Robertson, and Mustafa Ali Akin. "Early Retinal Findings Following Cooling in Neonatal Encephalopathy." Neuropediatrics 50, no. 01 (2018): 015–21. http://dx.doi.org/10.1055/s-0038-1669425.
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Background and Aim Perinatal HI (hypoxia–ischemia)-related visual defects including blindness are known to be associated with ischemic lesions in intracerebral visual pathways and ischemic retinal damage (IRD). Intraocular hemorrhages (IOH) such as retinal hemorrhage (RH), which may result from perinatal HI, can cause IRD by various mechanisms. We aimed to evaluate the early retinal findings in neonates with moderate-to-severe neonatal encephalopathy (NE) who underwent TH and its relationship between coagulation status, amplitude-integrated electroencephalography (aEEG) patterns, and magnetic resonance imaging–magnetic resonance spectroscopy (MRI–MRS) findings. Method and Patients A total of 31 newborn infants who underwent moderate-to-severe NE and TH included in the study. Coagulation parameters were taken immediately before starting TH, and daily during TH period. aEEG records were obtained during TH and rewarming period.Binocular indirect ophthalmoscopic examination (BIOE) and MRI–MRS scanning were performed when TH protocol completed. Results Total 13 (41.9%) patients had abnormal BIOE findings. Ten of them were (77%) IOH, other findings are as follows: RH (n = 7), optic disc hemorrhage (n = 2), and vitreous hemorrhage (n = 1). Initial coagulation status was not related to IOH. Worsened aEEG and MRI–MRS results were not related to BIOE findings. Conclusion Frequency of IOH is high in newborns with NE who underwent TH being independent from severity of MRS–MRI findings, aEEG pattern, and disturbed coagulation status.
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Wang, Qidong, Chuangen Guo, Lan Zhang, et al. "BOLD MRI to evaluate early development of renal injury in a rat model of diabetes." Journal of International Medical Research 46, no. 4 (2018): 1391–403. http://dx.doi.org/10.1177/0300060517743826.
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Objective To investigate changes in renal oxygenation levels by blood-oxygenation-level dependent (BOLD)-magnetic resonance imaging (MRI), and to evaluate BOLD-MRI for detecting early diabetic renal injury. Methods Seventy-five rats, with unilateral nephrectomy, were randomly divided into streptozotocin-induced diabetes mellitus (DM, n = 65) and normal control (NC, n = 10) groups. BOLD-MRI scans were performed at baseline (both groups) and at 3, 7, 14, 21, 28, 35, 42, 49, 56, 63 and 70 days (DM only). Renal cortical (C) and medullary (M) R2* signals were measured and R2* medulla/cortex ratio (MCR) was calculated. Results DM-group CR2* and MR2* values were significantly higher than NC values following diabetes induction. R2* values increased gradually and peaked at day 35 (CR2*, 33.95 ± 0.34 s–1; MR2*, 43.79 ± 1.46 s–1), then dropped gradually (CR2*, 33.17 ± 0.69 s–1; MR2*, 41.61 ± 0.95 s–1 at day 70). DM-group MCR rose gradually from 1.12 to 1.32 at day 42, then decreased to 1.25 by day 70. Conclusions BOLD-MRI can be used to non-invasively evaluate renal hypoxia and early diabetic renal injury in diabetic rats. MCR may be adopted to reflect dynamic changes in renal hypoxia.
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Qayyum, Aliya, Rony Avritscher, Rizwan Aslam, et al. "Immune checkpoint blockade (ICB) response evaluation with MRI/MR elastography (MRE) in surgical and nonsurgical patients with HCC." Journal of Clinical Oncology 38, no. 4_suppl (2020): 480. http://dx.doi.org/10.1200/jco.2020.38.4_suppl.480.
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480 Background: Currently, there is a lack of imaging biomarkers of immunotherapy outcome in hepatocellular carcinoma (HCC). The study aim was to determine if HCC enhancement on MRI and stiffness change measured by magnetic resonance elastography (MRE) can predict immunotherapy response. Methods: This was a prospective, Institutional Review Board approved study of 38 patients with HCC treated with immune checkpoint blockade (ICB) therapy. All patients had liver MRI/MRE and HCC biopsy at baseline, and MRI/MRE with biopsy or resection after 6 weeks therapy. HCC stiffness (kPa) was measured on MRE elastograms (liver stiffness maps). HCC enhancement and change in stiffness were compared with treatment response to ICB in 1) non-surgical patients (pembrolizumab), and 2) surgical patients (nivolumab +/- ipilimumab). For non-surgical patients, treatment response was defined as overall survival >1 year. For surgical patients, treatment response was defined as <50% viable tumor at time of resection. Analysis was performed using descriptive statistics and Spearman correlation; p-value <0.05 was considered statistically significant. Results: Twenty-five patients were evaluable. Median age was 67 years (32, 78). Etiology of liver disease was NASH (n=8), HCV (n=8), HBV (n=2) and unknown (n=7). Treatment response occurred in 11/25 (44%) patients. Median HCC size and change in size were 4.7 cm (1.2, 14.0) and –0.32 cm, respectively. Median baseline HCC stiffness and change in stiffness were 5 kPa (2.2, 12.4) and –0.1 kPa (–2.2, 1.5), respectively. Median change in HCC size for responders and non-responders was –1.2 cm (–4.8, 0.4) and 0 cm (–1.5, 1.1), respectively (p = 0.02). Treatment response was associated with absence of portal venous phase capsular enhancement and increase in HCC stiffness, (p<0.001). Conclusions: Capsular enhancement and MRE stiffness change may be useful biomarkers of immune cell activated response to ICB therapy.
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Meinel, Thomas Raphael, Johannes Kaesmacher, Pascal John Mosimann, et al. "Association of initial imaging modality and futile recanalization after thrombectomy." Neurology 95, no. 17 (2020): e2331-e2342. http://dx.doi.org/10.1212/wnl.0000000000010614.
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ObjectiveTo test the hypothesis that selection by initial imaging modality (MRI vs CT) is associated with rate of futile recanalizations (FRs) after mechanical thrombectomy (MT), we assessed this association in a multicenter, retrospective observational registry (BEYOND-SWIFT [Registry for Evaluating Outcome of Acute Ischemic Stroke Patients Treated With Mechanical Thrombectomy], NCT03496064).MethodsIn 2,011 patients (49.7% female, median age 73 years [61–81]) included between 2009 and 2017, we performed univariate and multivariate analyses regarding the occurrence of FR. FRs were defined as 90-day modified Rankin Scale (mRS) score 4–6 despite successful recanalization in patients selected by MRI (n = 690) and CT (n = 1,321) with a sensitivity analysis considering only patients with mRS 5–6 as futile.ResultsMRI as compared to CT resulted in similar rates of subsequent MT (adjusted odds ratio [aOR] 1.048, 95% confidence interval [CI] 0.677–1.624). Rates of FR were as follows: 571/1,489 (38%) FR mRS 4–6 including 393/1,489 (26%) FR mRS 5–6. CT-based selection was associated with increased rates of FRs compared to MRI (44% [41%–47%] vs 29% [25%–32%], p < 0.001; aOR 1.77 [95% CI 1.25–2.51]). These findings were robust in sensitivity analysis. MRI-selected patients had a delay of approximately 30 minutes in workflow metrics in real-world university comprehensive stroke centers. However, functional outcome and mortality were more favorable in patients selected by MRI compared to patients selected with CT.ConclusionsCT selection for MT was associated with an increased risk of FRs as compared to MRI selection. Efforts are needed to shorten workflow delays in MRI patients. Further research is needed to clarify the role of the initial imaging modality on FR occurrence and to develop a reliable FR prediction algorithm.
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Chander, Ashima, Peeyush Dhagat, Debraj Sen, and Harkirat Singh. "Evaluation of Contrast-Enhanced Magnetic Resonance Imaging and Spectroscopy as Diagnostic Tests to Differentiate Tumour Progression versus Post-Treatment Changes in Adult Gliomas and Their Correlation with Single-Photon Emission Computed Tomography - A Cross-Sectional Study from a Tertiary Care Centre in Pune, India." Journal of Evidence Based Medicine and Healthcare 8, no. 18 (2021): 1311–18. http://dx.doi.org/10.18410/jebmh/2021/250.
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BACKGROUND The differentiation of tumour progression from treatment-induced changes is critical in evaluating response to therapy among patients with gliomas. Although conventional magnetic resonance imaging (MRI) is invaluable in the overall assessment of such lesions, it is often difficult to differentiate between these two entities. We wanted to evaluate the role of contrast-enhanced MRI (CE MRI) and magnetic resonance spectroscopy (MRS) and correlation with 99 m Tc Sestamibi single-photon emission tomography (SPECT) in differentiating tumour progression from post-therapy changes in patients with glioma. METHODS This was a cross-sectional study. Being a rare disease, all adult patients (25 in number) with brain glioma reporting to the hospital for over a period of 12 months were included in the study. CE MRI, MRS and SPECT were performed at three months, six months and 12 months’ post-surgery and radiotherapy. The ratios for choline (Cho) / N-acetyl aspartate (NAA) and choline (Cho) creatine (Cr) were obtained from the areas suspicious for tumour progression on CE MRI and were correlated with the presence or absence of uptake on SPECT. These findings were correlated with the patients’ clinical course and tumour histopathology. RESULTS Both choline (Cho) / N-acetyl aspartate (NAA) and choline (Cho) / creatine (Cr) ratios had high detection rates for tumour progression when cut-off values of > 1.75 were used. For the Cho / NAA ratio, the sensitivity and specificity were 93.7 % and 100 %, respectively. The sensitivity and specificity for the Cho / Cr ratio were 81.3 % and 88.9 %, respectively. The sensitivity and specificity of 99 m Tc Sestamibi SPECT were 87.5 % and 100 %, respectively. CONCLUSIONS MRS and SPECT have high sensitivity and specificity for diagnosing tumour progression and must be used in conjunction with conventional CE MRI in the posttherapy setting. KEYWORDS Glioma, Progression, Post-Therapy Changes, MRI, MRS, SPECT
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Hong, Chih-Kai, Fa-Chuan Kuan, Kai-Lan Hsu, et al. "Does using high-tensile strength tape improve the fixation strength in tendon graft fixation with needleless suture wrapping techniques compared to a suture?" Journal of Orthopaedic Surgery 28, no. 3 (2020): 230949902097186. http://dx.doi.org/10.1177/2309499020971865.
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Purpose: To compare the biomechanical properties of a high-tensile strength suture and high-tensile strength tape in tendon graft fixation using two needleless suture wrapping techniques, the modified Prusik knot and modified rolling hitch. Methods: Two needleless suture wrapping techniques, the modified rolling hitch (MR) and modified Prusik knot (MP), were utilized. Meanwhile, two kinds of suture materials, a No. 2 braided nonabsorbable high-strength suture (S) and a 1.3 mm high-tensile strength tape (T), were used. A total of 40 porcine tendons were used, which were randomly divided into four groups. Each group was assigned to one of the following groups: MRS, MRT, MPS, and MPT. Each specimen was pretensioned to 100 N for three cycles, cyclically loaded from 50 to 200 N for 200 cycles, and finally loaded to failure. Results: The MRT group (34.1 ± 3.5%) had a significantly higher value compared with the MRS (29.7 ± 2.3%), MPS (27.1 ± 3.6%) and MPT (29.5 ± 4.0%) groups in term of elongation after cyclic loadings ( p = 0.002). In terms of ultimate failure load, there were no significant differences in the MRS (401 ± 27 N), MRT (380 ± 27 N), MPS (398 ± 44 N) and MPT (406 ± 49 N) values ( p = 0.539). All specimens failed due to suture breakage at the knots. Conclusion: Compared with the high-tensile strength suture, using the high-tensile strength tape lead to greater elongation after cyclic loading when the modified rolling hitch was used. No differences in terms of elongation after cyclic loading and load to failure were found between the high-tensile strength suture and tape using the modified Prusik knot.
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Meyerhoff, D. J. "Spectroscopic imaging of human disease." Proceedings, annual meeting, Electron Microscopy Society of America 54 (August 11, 1996): 884–85. http://dx.doi.org/10.1017/s0424820100166889.
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Magnetic Resonance Imaging (MRI) observes tissue water in the presence of a magnetic field gradient to study morphological changes such as tissue volume loss and signal hyperintensities in human disease. These changes are mostly non-specific and do not appear to be correlated with the range of severity of a certain disease. In contrast, Magnetic Resonance Spectroscopy (MRS), which measures many different chemicals and tissue metabolites in the millimolar concentration range in the absence of a magnetic field gradient, has been shown to reveal characteristic metabolite patterns which are often correlated with the severity of a disease. In-vivo MRS studies are performed on widely available MRI scanners without any “sample preparation” or invasive procedures and are therefore widely used in clinical research. Hydrogen (H) MRS and MR Spectroscopic Imaging (MRSI, conceptionally a combination of MRI and MRS) measure N-acetylaspartate (a putative marker of neurons), creatine-containing metabolites (involved in energy processes in the cell), choline-containing metabolites (involved in membrane metabolism and, possibly, inflammatory processes),
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Champlin, Grace, Scott Hwang, Guolian Kang, et al. "Progression of Central Nervous System Vasculopathy in Young Adults with Sickle Cell Anemia." Blood 134, Supplement_1 (2019): 2290. http://dx.doi.org/10.1182/blood-2019-129193.
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Introduction Silent cerebral infarcts (SCI) and cerebral vessel stenosis are common and progressive in sickle cell anemia (SCA). Most data regarding brain lesions in SCA are cross-sectional or derive from pediatric cohorts with short follow-up not spanning the transition into adulthood. While hydroxyurea and transfusions may reduce the incidence of SCI and abnormal transcranial Doppler (TCD) in children with SCA, data on the effectiveness of these therapies in young adults are lacking. We tested the hypothesis that SCI and cerebral vessel stenosis progressed in young adults with SCA, relative to their childhood years. In addition, we explored the relationship between progression of brain vasculopathy and exposure to disease-modifying therapy. Methods We obtained brain magnetic resonance imaging (MRI) and MR angiography (MRA) in adults with SCA (HbSS or HbSβ0-thalassemia) on chronic transfusions or hydroxyurea. Participants were recruited from the IRB-approved longitudinal cohort study, Sickle Cell Clinical Research and Intervention Program (Hankins et al., PBC 2018). Participants were ages 18.0 to 32.0 at adult imaging and had at least one prior MRI/MRA between 0 and 17.9 years. Pediatric MRI/MRAs were performed for clinical indications (e.g., neurologic concern). All pediatric and adult MRI/MRAs had similar imaging protocols and were centrally reviewed by a neuroradiologist. SCIs were defined as focal T2-weighted or FLAIR hyperintensity. MRIs were considered abnormal if SCI or overt strokes were present. MRI progression was defined as new SCI or new overt strokes. Vessel stenoses were graded using a validated vasculopathy scale from 0 to 6 (Helton et al., Blood 2014). Abnormal MRA was defined as a score ≥1 and progression as any increase in the vasculopathy grading. We retrospectively ascertained childhood TCDs, treatments, overt strokes, and transient ischemic attacks (TIA, <24 hours neurologic symptoms with no imaging change). The proportion of abnormal brain MRI/MRA was calculated for the participants' pediatric (0-11.9), adolescent (12.0-17.9), and young adult (18.0-32.0) years and compared using multivariate generalized linear mixed model. Multivariate logistic regression investigated the association of exposure to hydroxyurea or chronic transfusion with MRI/MRA progression from child to adulthood. Results Forty-one young adults with SCA, all African American, median age 19.0 years, (range 18.0-31.5) were included (Table 1). All received disease-modifying therapy prior to adult MRI/MRA; median duration of hydroxyurea was 10.4 years (range, 0.3 to 20.35) and chronic transfusion was 9.2 years (range, 2.5 to 14.6). Indications for chronic transfusion were: abnormal TCD (N=6), overt stroke (N=4), recurrent vaso-occlusive events (VOE) (N=1), and chronic kidney disease (N=1). Indications for hydroxyurea were: VOE (N=27), overt stroke (N=1), and abnormal TCD (N=1). The total follow-up time from pediatric to adult brain MRI/MRA was 804 person-years, during which 2 patients had new strokes and 5 had TIAs. Progression of MRI and MRA occurred in 12 (29%) and 8 (20%) young adults, respectively, in relation to their pediatric exams (p=0.04 and p=0.01), both among hydroxyurea (Figure 1a) and transfusion (Figure 1b) groups. Both MRI and MRA progression occurred more frequently among those with prior stroke or conditional or abnormal TCD velocities, p=0.015. Controlling for age at adult imaging, exposure to hydroxyurea was associated with decreased probability of MRI progression (OR=0.05, 95%CI: 0.01~0.52, p=0.01), but not MRA (OR=0.22, 95%CI: 0.02~2.34, p=0.2). When further adjusting for transfusions, exposure to hydroxyurea was still associated with decreased probability of MRI progression (OR=0.05, 95%CI: 0.4~0.64, p=0.021) but not transfusions (OR 0.94, 95%CI: 0.16~5.39, p=0.95). Conclusion Close to a quarter of young adults with SCA treated with disease-modifying therapies for approximately a decade, experienced progression of brain lesions despite treatment with disease-modifying therapies. Among patients exposed to hydroxyurea, less progression of SCIs occurred. Overt stroke or TCD elevation in childhood increased the risk of brain lesion progression. In children with SCA, the presence of SCI and vessel stenosis in childhood should prompt consideration of alternative treatments given the evidence that brain lesions progress as they emerge into adulthood. Disclosures Kang: MBIO: Other: St. Jude Children's Research Hospital has an existing exclusive license and ongoing partnership with Mustang Bio for the further clinical development and commercialization of this XSCID gene therapy. Estepp:Forma Therapeutics: Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; Eli Lilly and Co: Research Funding; Pfizer: Research Funding; Esperion: Consultancy. Ataga:Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Modus Therapeutics: Honoraria; Emmaus Life Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. King:Incyte: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novimmune: Research Funding; Cell Works: Consultancy; Bioline: Consultancy; Celgene: Consultancy; Amphivena Therapeutics: Research Funding; Tioma Therapeutics (formerly Vasculox, Inc.):: Consultancy; RiverVest: Consultancy; WUGEN: Equity Ownership. Wang:Agios Pharmaceuticals: Consultancy; Novartis: Consultancy. Hankins:NHLBI: Honoraria; ASPHO: Honoraria; Novartis: Research Funding; LYNKS Foundation: Research Funding; Bluebird Bio: Consultancy; NHLBI: Research Funding; Global Blood Therapeutics: Research Funding; National Committee for Quality Assurance: Consultancy.
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Kang, Huining, Edward J. Bedrick, I.-Ming Chen, et al. "Molecular Classifiers for Prediction of Minimal Residual Disease (MRD) and Event Free Survival (EFS) Improve Risk Assignment at Diagnosis in Pediatric High-Risk B Precursor Acute Lymphoblastic Leukemia (ALL): A Children’s Oncology Group Study." Blood 110, no. 11 (2007): 1422. http://dx.doi.org/10.1182/blood.v110.11.1422.1422.
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Abstract Gene expression profiling has significant potential to improve risk classification and therapeutic targeting in ALL. Our goal is to develop molecular classifiers that more reliably predict relapse or resistance to current treatment regimens in order to identify patients who may benefit from therapeutic intensification or experimental approaches. COG P9906, testing an augmented BFM regimen, enrolled 271 patients with B precursor ALL with NCI high risk features (older age/higher WBC) who had experienced very poor outcomes (45% EFS) on prior trials. Patients with favorable (trisomy 4+10/TEL-AML1) or very unfavorable (Ph+/hypodiploidy) genetics were excluded. Expression profiles (Affymetrix HG_U133Plus2) were obtained from pre-treatment leukemic blasts in 207/271 (76%) children on COG P9906; these 207 cases were representative of the overall cohort. EFS at 4 yrs was 61% and flow cytometric measures of MRD (flow MRD) at end-induction (day 28) were highly predictive of outcome. Using expression profiles, a molecular classifier predictive of EFS was modeled using a Cox regression-based supervised principal components analysis and modified score test with extensive nested cross validation. A 42 gene molecular classifier predictive of EFS differentiated this cohort into a low (4 yr EFS: 81%, n=109) and high (4 yr EFS: 50%, n=98) molecular risk group (log rank test, P< 0.0001). In multivariate analysis, the molecular risk classifier (MRC) retained prognostic significance (likelihood ratio test, p=0.0001) when adjusted for flow MRD and WBC. The best predictive model for EFS resulted when the MRC was combined with flow MRD; the resulting low (MRC low risk, MRD-; 87% EFS), medium (MRC low risk, MRD+ or MRC high risk, MRD-; 62% EFS), and high risk (MRC high risk, MRD+; 29% EFS) groups had significant outcome differences (Fig. A). As one must wait until the end of induction to obtain flow MRD to apply the combined classifier, we next determined if we could develop a molecular classifier to predict end-induction MRD in pre-treatment samples. Using a modified t-test and diagonal linear discriminant analysis with extensive cross validation, we derived a 23 gene molecular classifier predictive of end-induction MRD (ROC Accuracy: 0.80; p <0.0001). When the molecular classifier for MRD was combined with the molecular classifier for EFS, three distinct risk groups with significantly different outcomes were similarly defined (low risk: 82% EFS, medium risk: 63% EFS; high risk: 45% EFS; Fig. B). These studies demonstrate that molecular classifiers for EFS and MRD significantly enhance risk prediction in high risk B-ALL and may allow earlier intervention in induction in particularly high risk patients. Use of molecular classifiers to modify risk-adapted therapy has the highest priority in evaluating strategies to improve outcome in children with ALL and are currently being prospectively tested in COG trials. Figure Figure
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Quan, Guanmin, Kexin Zhang, Yawu Liu, et al. "Role of Dynamic Susceptibility Contrast Perfusion MRI in Glioma Progression Evaluation." Journal of Oncology 2021 (February 9, 2021): 1–9. http://dx.doi.org/10.1155/2021/1696387.
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Accurately and quickly differentiating true progression from pseudoprogression in glioma patients is still a challenge. This study aims to explore if dynamic susceptibility contrast- (DSC-) MRI can improve the evaluation of glioma progression. We enrolled 65 glioma patients with suspected gadolinium-enhancing lesion. Longitudinal MRI follow-up (mean 590 days, range: 210–2670 days) or re-operation (n = 3) was used to confirm true progression (n = 51) and pseudoprogression (n = 14). We assessed the diagnostic performance of each MRI variable and the different combinations. Our results showed that the relative cerebral blood volume (rCBV) in the true progression group (1.094, 95%CI: 1.135–1.636) was significantly higher than that of the pseudoprogression group (0.541 ± 0.154) p < 0.001 . Among the 18 patients who had serial DSC-MRI, the rCBV of the progression group (0.480, 95%CI: 0.173–0.810) differed significantly from pseudoprogression (-0.083, 95%CI: −1.138–0.620) group p = 0.015 . With an rCBV threshold of 0.743, the sensitivity and specificity for discriminating true progression from pseudoprogression were 76.5% and 92.9%, respectively. The Cho/Cr and Cho/NAA ratios of the true progression group (2.520, 95%CI: 2.331–2.773; 2.414 ± 0.665, respectively) were higher than those of the pseudoprogression group (1.719 ± 0.664; 1.499 ± 0.500, respectively) ( p = 0.001 , p < 0.001 , respectively). The areas under ROC curve (AUCs) of enhancement pattern, MRS, and DSC-MRI for the differentiation were 0.782, 0.881, and 0.912, respectively. Interestingly, when combined enhancement pattern, MRS, and DSC-MRI variables, the AUC was 0.965 and achieved sensitivity 90.2% and specificity 100.0%. Our results suggest that DSC-MRI can significantly improve the diagnostic performance for identifying glioma progression. DSC-MRI combined with conventional MRI may promptly distinguish true gliomas progression from pseudoprogression when the suspected gadolinium-enhancing lesion was found, without the need for a long-term follow-up.
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Bernaudin, Francoise, Suzanne Verlhac, Lena COIC, Emmanuelle Lesprit, Pierre Brugieres, and Philippe Reinert. "Long Term Follow-Up of Pediatric SCD Patients with Abnormal High Velocities on Transcranial Doppler: Monocenter Experience in Creteil, France." Blood 104, no. 11 (2004): 1656. http://dx.doi.org/10.1182/blood.v104.11.1656.1656.
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Abstract Abnormal high velocities are predictive of high stroke risk which can be significantly reduced by transfusion program (Adams and al). They are related to stenosis, severe anemia or tissue hypoxia. We hypothesized that high velocities observed in patients with normal MRA and normalized on transfusion program (TP), were anemia related and could be safely decreased with hydroxyurea (HU)-therapy. Patients and Methods: since 1992, 291 pediatric SCD patients (235 SS, 40 SC, 3 Sb0, 11 Sb+) were systematically explored once a year by TCD. The newborn screened cohort (n=149) had the first TCD exploration between 12 and 18 months age. TCD was performed with a real-time imaging unit, using a 2 MHz sector transducer with color Doppler capabilities. When abnormal high velocities (defined as mean maximum velocities > 200 cm/sec in MCA, ACA or ICA) were observed, TCD was controlled and the patient treated with TP and cerebral imaging (MRI/MRA) was performed within 3 months. In patients with severe stenosis, TP was pursued or transplantation performed. In patients with normal MRA and transfusion-normalized velocities, a progressive switch towards HU therapy was applied and TCD controlled once a trimester. Results: among the stroke-free patients (n=281), abn. high velocities were detected in 25 patients (all SS:11% of incidence in SS patients). In the newborn screened population, velocities became abnormal in 10 patients at the median age of 5.7 years (range 1.4 – 12.5 y). The first MRI/MRA (n=24/25) performed in the 3 months following the detection of high velocities showed MRI/silent infarcts in 9/24 (38%): only 1/11 among the newborn screened cohort had silent infarcts in contrast with 8/13 older patients secondary referred in our center. MRA detected severe vascular abnormalities in 10 and mild in 3 patients. Mean velocities (2.69 m/sec) were significantly higher (p=0.002) in the 7 patients with abn. MRI and MRA than in the 10 patients (2.11m/sec) who had normal MRI and MRA. One stroke occurred in a very young 1.6 y old girl just before the second TCD evaluation (first abn. TCD had been observed at 1.5 y) and before the beginning of the TP. Long-term outcome: no stroke was observed following the initiation of the TP. With a median follow-up of 4.4 years (0.5 to 11.4 y.), velocities remained abnormal in 11/25 patients: 7 of them had abnormal MRA and among the 4 patients with normal MRA at first exploration MRA became abnormal in 2 cases showing that abnormal TCD can precede the occurrence of cerebral vasculopathy. TP was maintained in 7 patients and safely stopped in 4 patients transplanted with genoidentical donor. Velocities normalization (defined as < 170 cm/sec) was observed in 13/25 patients in a median delay of 0.75 years (0.25 – 2.3 years). TP was stopped in 10 patients with normal MRA and therapy was switched towards HU in 7 patients with abstention in 3. However, abnormal TCD relapsed in 4 patients who were again placed on TP. Conclusion: abnormal high velocities concerned 11% of SS patients and were predictive of MRA and MRI lesions occurrence. TP was efficient to prevent the stroke risk and normalized velocities in about 50% of patients but relapses were observed in 4/7 patients following TP stop and HU switch. Only few patients with high velocities history did not develop cerebral vasculopathy. Also, early TCD allows a selection of very high risk patients justifying the research of suitable donors.
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Ozturk, Kerem, Esra Soylu, and Mufit Parlak. "Dural venous sinus thrombosis: The combination of noncontrast CT, MRI and PC-MR venography to enhance accuracy." Neuroradiology Journal 31, no. 5 (2018): 473–81. http://dx.doi.org/10.1177/1971400918781969.
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Aim The aim of this article is to determine whether a combination of noncontrast CT (NCCT), three-dimensional-phase contrast magnetic resonance venography (3D PC-MRV), T1- and T2-weighted MRI sequences can help to identify acute and subacute dural venous sinus thrombosis (DVST) with greater accuracy. Methods A total of 147 patients with DVST ( n = 30) and a control group ( n = 117) underwent NCCT, T1- and T2-weighted MRI sequences, and 3D PC-MRV from 2012 to 2016. Two experienced observers interpreted the images retrospectively for the presence of DVST. Nonvisualization of the dural venous sinuses on 3D PC-MRV and signal changes supporting acute or subacute thrombus on T2- and T1-weighted images were considered a direct sign of DVST. Also, using circle region of interest (ROI) techniques, attenuation measurement from each sinus was obtained on NCCT. Sensitivity and specificity were computed for these modalities separately and in combination for diagnosis of DVST using digital subtraction angiography as the reference standard. Results Nonvisualization of venous sinuses on 3D PC-MRV (sensitivity 100%, specificity 71%) in combination with both applying Hounsfield unit (HU) threshold values of greater than 60 on NCCT (sensitivity 70%, specificity 94%) and acquiring signal changes supporting DVST on T2- and T1-weighted images (sensitivity 83%, specificity 96%), were found to have 100% sensitivity and 100% specificity in the identification of acute or subacute DVST. Conclusion The combination of NCCT, T1- and T2-weighted MRI and 3D PC-MRV may allow the diagnosis of acute or subacute DVST and may obviate the need for contrast usage in patients with renal impairment or contrast allergies.
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Nottage, Kerri, Russell E. Ware, Matthew P. Smeltzer, et al. "Brain MRI/MRA Findings after Hydroxyurea Treatment in Children with Sickle Cell Anemia." Blood 124, no. 21 (2014): 89. http://dx.doi.org/10.1182/blood.v124.21.89.89.
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Abstract Background: Up to 40% of children with sickle cell anemia (SCA) will have abnormalities on brain imaging due to their hematologic disorder, much of which is subclinical. Common abnormalities on brain magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) include leukoencephalopathy from microvascular ischemic insult and vascular stenosis from endothelial damage. Silent cerebral ischemic insults are progressive; further neurologic abnormalities, including overt stroke, are more common among children with ischemic findings on MRI compared to children without them. Furthermore, poor performance on neuropsychological testing, lower IQ, and higher rates of grade retention are common in children with SCA and cerebral ischemic disease. The effect of hydroxyurea treatment on the development and progression of vascular stenosis and leukoencephalopathy is unclear. This study aimed to longitudinally evaluate the development of intracerebral abnormalities through serial MRI/MRA in children with SCA (HbSS and HbSβ0-thalassemia) who receive long-term therapy with hydroxyurea. Methods: Children with SCA and no prior history of overt stroke enrolled in the Hydroxyurea Study of Long-Term Effects (HUSTLE NCT00305175) underwent brain MRI/MRA, transcranial doppler (TCD) examinations, and laboratory evaluations immediately before hydroxyurea initiation and after 3 and 6 years of treatment to maximum tolerated dose. MRI/MRAs were reviewed for the presence or absence of vascular stenosis and leukoencephalopathy. Leukoencephalopathy was defined as white matter T2 hyperintensity. Proportions of abnormal MRI/MRA findings were compared between baseline and 3 years and baseline and 6 years using McNemar’s test and the Wilcoxon-Mann-Whitney exact test was used to explore associations with laboratory parameters. Results: Forty-six children with SCA, mean age 9.4 years (range 1-17.3), had an MRI/MRA at baseline and 3 years post-initiation of hydroxyurea. Ten children had an additional MRI/MRA after 6-years of hydroxyurea therapy. Frequencies of leukoencephalopathy and vascular stenosis are shown in the table. Prevalence of leukoencephalopathy before hydroxyurea therapy was higher than that reported in the literature for untreated children with SCA of similar age. There were no significant differences between baseline imaging findings and those at 3 and 6 years. Table: Prevalence of leukoencephalopathy and vascular stenosis at baseline, 3 and 6 years Baseline (n=47) Median age 9.6 years (range 1.0 to 17.3) 3 years (n=46) Median age 13.1 years (range 4.4 to 21.1) 6 years (n=10) Median age 14.5 years (range 8.3 to 18.3) Leukoencephalopathy 27 (57.4%) 28 (60.9%)* 5 (50%)* Stenosis 3 (6.4%) 1 (2.2%)* 0 *all p>0.05 Children with leukoencephalopathy at baseline and 3 years were older than those without (mean 10.7 vs. 7.7 years, p=0.01; 10.5 vs. 7.5 years, p=0.02 respectively). Lower HbF at baseline was associated with the presence of leukoencephalopathy at year 3 (median HbF 4.6% vs. 12.4%, p=0.008), but there was no association between HbF at 3-years and the presence of leukoencephalopathy at 3-years (median HbF 16.4% vs. 13.2%, p=0.55). When stratified by age, these findings were similar. TCD velocities and other hematologic parameters were not associated with MRI/MRA abnormalities. The small number of vascular stenosis cases precluded further analyses of this outcome. Conclusions: In this longitudinal study, children treated with hydroxyurea for 3-6 years did not demonstrate an increased frequency of vascular stenosis or leukoencephalopathy on brain MRI/MRA during treatment. Older age at hydroxyurea initiation and lower pre-hydroxyurea HbF percentage were associated with the presence of leukoencephalopathy at baseline and 3-years. These findings suggest that hydroxyurea may mitigate the expected progression of vascular stenosis and leukoencephalopathy in children with SCA, and that this therapy should be initiated early on, before the development of cerebrovascular disease, particularly among those with a low HbF percentage. Disclosures Off Label Use: hydroxyurea for children with sickle cell disease.
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Brimkulov, Ulan. "Matrices whose inverses are tridiagonal, band or block-tridiagonal and their relationship with the covariance matrices of a random Markov process." Filomat 33, no. 5 (2019): 1335–52. http://dx.doi.org/10.2298/fil1905335b.
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The article discusses the matrices of the form A1n, Amn, AmN, whose inverses are: tridiagonal matrix A-1n (n - dimension of the A-mn matrix), banded matrix A-mn (m is the half-width band of the matrix) or block-tridiagonal matrix A-m N (N = n x m - full dimension of the block matrix; m - the dimension of the blocks) and their relationships with the covariance matrices of measurements with ordinary (simple) Markov Random Processes (MRP), multiconnected MRP and vector MRP, respectively. Such covariance matrices frequently occur in the problems of optimal filtering, extrapolation and interpolation of MRP and Markov Random Fields (MRF). It is shown, that the structures of the matrices A1n, Amn, AmN have the same form, but the matrix elements in the first case are scalar quantities; in the second case matrix elements represent a product of vectors of dimension m; and in the third case, the off-diagonal elements are the product of matrices and vectors of dimension m. The properties of such matrices were investigated and a simple formulas of their inverses were found. Also computational efficiency in the storage and the inverse of such matrices have been considered. To illustrate the acquired results, an example on the covariance matrix inversions of two-dimensional MRP is given.
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EKŞİ, Ziya, Murat ÇAKIROĞLU, Cemil ÖZ, Ayse ARALAŞMAK, Hasan Hüseyin KARADELİ, and Muhammed Emin ÖZCAN. "Differentiation of relapsing-remitting and secondary progressive multiple sclerosis: a magnetic resonance spectroscopy study based on machine learning." Arquivos de Neuro-Psiquiatria 78, no. 12 (2020): 789–96. http://dx.doi.org/10.1590/0004-282x20200094.
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ABSTRACT Introduction: Magnetic resonance imaging (MRI) is the most important tool for diagnosis and follow-up in multiple sclerosis (MS). The discrimination of relapsing-remitting MS (RRMS) from secondary progressive MS (SPMS) is clinically difficult, and developing the proposal presented in this study would contribute to the process. Objective: This study aimed to ensure the automatic classification of healthy controls, RRMS, and SPMS by using MR spectroscopy and machine learning methods. Methods: MR spectroscopy (MRS) was performed on a total of 91 participants, distributed into healthy controls (n=30), RRMS (n=36), and SPMS (n=25). Firstly, MRS metabolites were identified using signal processing techniques. Secondly, feature extraction was performed based on MRS Spectra. N-acetylaspartate (NAA) was the most significant metabolite in differentiating MS types. Lastly, binary classifications (healthy controls-RRMS and RRMS-SPMS) were carried out according to features obtained by the Support Vector Machine algorithm. Results: RRMS cases were differentiated from healthy controls with 85% accuracy, 90.91% sensitivity, and 77.78% specificity. RRMS and SPMS were classified with 83.33% accuracy, 81.81% sensitivity, and 85.71% specificity. Conclusions: A combined analysis of MRS and computer-aided diagnosis may be useful as a complementary imaging technique to determine MS types.
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Rozell, CL, WL Sibbitt, and WM Brooks. "Structural and Neurochemical Markers of Brain Injury in the Migraine Diathesis of Systemic Lupus Erythematosus." Cephalalgia 18, no. 4 (1998): 209–15. http://dx.doi.org/10.1046/j.1468-2982.1998.1804209.x.
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Objective: To determine whether migraine in systemic lupus erythematosus (SLE) is associated with accentuated brain injury and disease activity. Methods: Forty SLE patients (11 without headache, 11 with non-migraine headache, and 18 with migraine) underwent clinical evaluation, magnetic resonance imaging (MRI), and spectroscopy (MRS). Results: Recurrent headache occurred in 75% of SLE patients. MRI abnormalities and reduced N-acetylaspartate were common. However, migraine in SLE was not associated with increased disease activity or severity, neuropsychiatrie manifestations, or end-organ involvement compared to patients without migraine ( p>0.05). There were no differences in the prevalence or severity of MRI or MRS abnormalities between SLE patients with migraine, with non-migraine headache, or without headache ( p>0.05). Conclusions: Headache does not identify SLE patients at risk for brain injury, increased disease activity, or increased end-organ involvement. Aggressive immunosuppressive therapy for headache alone is not indicated in SLE.
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Oudeman, Jos, Filip Eftimov, Gustav J. Strijkers, et al. "Diagnostic accuracy of MRI and ultrasound in chronic immune-mediated neuropathies." Neurology 94, no. 1 (2019): e62-e74. http://dx.doi.org/10.1212/wnl.0000000000008697.
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ObjectiveTo assess and compare the diagnostic performance of qualitative and (semi-)quantitative MRI and ultrasound for distinguishing chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) from segmental spinal muscular atrophy (sSMA).MethodsPatients with CIDP (n = 13), MMN (n = 10), or sSMA (n = 12) and healthy volunteers (n = 30) were included. MRI of the brachial plexus, using short tau inversion recovery (STIR), nerve-specific T2-weighted (magnetic resonance neurography [MRN]), and diffusion tensor imaging (DTI) sequences, was evaluated. Furthermore, with ultrasound, cross-sectional areas of the nerves were evaluated. Three radiologists blinded for diagnosis qualitatively scored hypertrophy and increased signal intensity (STIR and MRN), and intraobserver and interobserver agreement was assessed. For the (semi-)quantitative modalities, group differences and receiver operator characteristics were calculated.ResultsHypertrophy and increased signal intensity were found in all groups including healthy controls. Intraobserver and interobserver agreements varied considerably (intraclass correlation coefficients 0.00–0.811 and 0.101–0.491, respectively). DTI showed significant differences (p < 0.05) among CIDP, MMN, sSMA, and controls for fractional anisotropy, axial diffusivity, and radial diffusivity in the brachial plexus. Ultrasound showed significant differences in cross-sectional area (p < 0.05) among CIDP, MMN, and sSMA in upper arm and brachial plexus. For distinguishing immune-mediated neuropathies (CIDP and MMN) from sSMA, ultrasound yielded the highest area under the curve (0.870).ConclusionQualitative assessment of hypertrophy and signal hyperintensity on STIR or MRN is of limited value. DTI measures may discriminate among CIDP, MMN, and sSMA. Currently, ultrasound may be the most appropriate diagnostic imaging aid in the clinical setting.
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Mullins, D., M. Lamar, E. Daly, et al. "Dementia in Alzheimer’s Disease: A Comparison of MRI and 1H-MRS Findings Between Alzheimer’s Disease and Mild Cognitive Impairment." European Psychiatry 24, S1 (2009): 1. http://dx.doi.org/10.1016/s0924-9338(09)70929-0.
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Aim:To compare Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (1H-MRS) between people with Alzheimer's disease (AD) and mild cognitive impairment (MCI).Background review:AD is characterised by cognitive impairment. 10-15% of people with MCI progress to dementia each year. The hippocampus is involved in memory functioning and is one of the brain regions first affected by AD. MRI based hippocampal volumetric measurement enables accurate quantification of atrophy. In addition, 1H-MRS can be used to measure concentrations of brain metabolites including myoinositol (mI) and N-acetylaspartate (NAA). NAA is a proxy measure of neuronal density.Method:Subjects with AD (n=46), MCI (n=28) and controls (n=39) were scanned using a 1.5 Tesla MR system. Manual tracing of hippocampal volumes was undertaken using Measure software. 1H-MRS voxels of interest were defined in the left and right hippocampi. A point-resolved spectroscopy pulse sequence produced spectra from each voxel and clearly resolved NAA and mI peaks. Statistical analysis was undertaken using SPSS15.Results:Hippocampal volumes were significantly reduced between AD and controls (p=0.003) and between AD and MCI (p=0.001). Compared to controls, individuals with AD and MCI had a significant reduction in [NAA]. MCI showed a non-significant increase in [mI]. A positive relationship was found between hippocampal volume and [NAA] and between hippocampal volume and [mI] for MCI.Conclusions:AD is associated with decreased viable neuronal density/function (as measured by NAA) and a reduction in hippocampal volume associated with impaired cognitive functioning. The elevated [mI] in MCI may be a “tipping point” into dementia.
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Bulik, Martin, Tomas Kazda, Pavel Slampa, and Radim Jancalek. "The Diagnostic Ability of Follow-Up Imaging Biomarkers after Treatment of Glioblastoma in the Temozolomide Era: Implications from Proton MR Spectroscopy and Apparent Diffusion Coefficient Mapping." BioMed Research International 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/641023.
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Objective. To prospectively determine institutional cut-off values of apparent diffusion coefficients (ADCs) and concentration of tissue metabolites measured by MR spectroscopy (MRS) for early differentiation between glioblastoma (GBM) relapse and treatment-related changes after standard treatment.Materials and Methods. Twenty-four GBM patients who received gross total resection and standard adjuvant therapy underwent MRI examination focusing on the enhancing region suspected of tumor recurrence. ADC maps, concentrations ofN-acetylaspartate, choline, creatine, lipids, and lactate, and metabolite ratios were determined. Final diagnosis as determined by biopsy or follow-up imaging was correlated to the results of advanced MRI findings.Results. Eighteen (75%) and 6 (25%) patients developed tumor recurrence and pseudoprogression, respectively. Mean time to radiographic progression from the end of chemoradiotherapy was 5.8 ± 5.6 months. Significant differences in ADC and MRS data were observed between those with progression and pseudoprogression. Recurrence was characterized byN-acetylaspartate ≤ 1.5 mM, choline/N-acetylaspartate ≥ 1.4 (sensitivity 100%, specificity 91.7%),N-acetylaspartate/creatine ≤ 0.7, and ADC ≤ 1300 × 10−6 mm2/s (sensitivity 100%, specificity 100%).Conclusion. Institutional validation of cut-off values obtained from advanced MRI methods is warranted not only for diagnosis of GBM recurrence, but also as enrollment criteria in salvage clinical trials and for reporting of outcomes of initial treatment.
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Alshammari, Qurain T., Mohammed Salih, Moawia Gameraddin, Mohamed Yousef, Bushra Abdelmalik, and Omer Loaz. "Accuracy of Magnetic Resonance Spectroscopy in Discrimination of Neoplastic and Non-Neoplastic Brain Lesions." Current Medical Imaging Formerly Current Medical Imaging Reviews 17, no. 7 (2021): 904–10. http://dx.doi.org/10.2174/1573405617666210224112808.
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Background: Differentiation of brain lesions by conventional MRI alone is not enough. The introduction of sophisticated imaging methods, such as MR Spectroscopy (MRS), will contribute to accurate differentiation. Objective: To determine the diagnostic accuracy of MRS in differentiating neoplasm and non-neoplastic brain lesion. Methodology: This is a cross-sectional descriptive study conducted at Khartoum State from the period of 2015 to 2017. Thirty cases with brain lesions were included in the study investigated with MRS (Single-voxel spectroscopy) and conventional MRI. A comparison of MRS findings and histopathologic analysis was performed. The ratios of Cho/Cr and Cho/NAA were analyzed and compared between neoplastic and non-neoplastic brain masses. Data were analyzed using SPSS version 23. Results: Out of the 30 patients affected with brain lesions, there were 16 females and 14 males with a mean age of 44 +- 18 years. The ratios of Cho/Cr and Cho/NAA were higher in gliomas, astrocytoma, and meningioma than non-neoplastic lesions. Kappa statistical value (K) showed a good agreement between MRS and histopathological analysis (K= 0.60). The diagnostic accuracy of MRS was 100%, with 82.60% sensitivity, 85.71% specificity, 95% PPV, and 60% NPV. Conclusion: MRS has high diagnostic accuracy in differentiating neoplasm from non-neoplastic brain tumors. The elevation ratios of Choline-to- N-acetyl aspartate and choline-to- creatine can help neurosurgeons and clinicians differentiate benign from malignant masses.
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Bouts, Mark J. R. J., Ivo A. C. W. Tiebosch, Annette van der Toorn, Jeroen Hendrikse, and Rick M. Dijkhuizen. "Lesion Development and Reperfusion Benefit in Relation to Vascular Occlusion Patterns after Embolic Stroke in Rats." Journal of Cerebral Blood Flow & Metabolism 34, no. 2 (2013): 332–38. http://dx.doi.org/10.1038/jcbfm.2013.202.
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Vascular occlusion sites largely determine the pattern of cerebral tissue damage and likelihood of subsequent reperfusion after acute ischemic stroke. We aimed to elucidate relationships between flow obstruction in segments of the internal carotid artery (ICA) and middle cerebral artery (MCA), and (1) profiles of acute ischemic lesions and (2) probability of subsequent beneficial reperfusion. Embolic stroke was induced by unilateral intracarotid blood clot injection in normotensive ( n=53) or spontaneously hypertensive ( n=20) rats, followed within 2 hours by magnetic resonance (MR) angiography (MRA), diffusion- (DWI) and perfusion-weighted magnetic resonance imaging (MRI) (PWI). In a subset of animals ( n=9), MRI was repeated after 24 and 168 hours to determine the predictive value of the occlusion pattern on benefit of reperfusion. The extent of cerebral perfusion and diffusion abnormality was related to the pattern of flow obstruction in ICA and MCA segments. Hypertensive animals displayed significantly larger cortical perfusion lesions. Acute perfusion-diffusion lesion mismatches were detected in all animals that subsequently benefitted from reperfusion. Yet, the presence of an angiography-diffusion mismatch was more specific in predicting reperfusion benefit. Combination of DWI, PWI, and MRA exclusively informs on the impact of arterial occlusion profiles after acute ischemic stroke, which may improve prognostication and subsequent treatment decisions.
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Satria, Rivananda Rama, U. Ubaidillah, and Fitrian Imaduddin. "Analytical Approach of a Pure Flow Mode Serpentine Path Rotary Magnetorheological Damper." Actuators 9, no. 3 (2020): 56. http://dx.doi.org/10.3390/act9030056.
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This paper has two main goals in the development of a novel flow-mode magnetorheological brake (MRB): (1) produce a mathematical model of a flow-mode MRB and (2) predict the torque density of the proposed MRB compared to the other type of MRB. In this design, the flow mode MRB is made by screw pump to make the Magnetorheological Fluid (MRF) flow through the radial and annular channel. The serpentine path flux is developed in the proposed MRB to make the annular channel an active region as well. With the proposed design concept, the work of a pure flow-mode serpentine path MRB can be accomplished. In this study, Finite Element Method Magnetics (FEMM) is used to calculate the magnetic field applied to the active regions and analytical approach used to obtain the output damping torque. The simulation results show that the magnetic fluxes flow through the radial channel and annular channel as well. The radial and annular channel is activated, which led to higher output damping torque. The mathematical modelling shows that the helical angle of the screw pump significantly affects the damping torque. The results show that the output damping torque density can be adjusted from 42.18 N/mm2 in the off-state with 0 rpm to around 40,518.96 N/mm2 at 20 rpm. The torque density of the proposed MRB is higher than the shear mode MRB.
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Rawstron, Andy C., J. Anthony Child, Ruth M. de Tute, et al. "Minimal Residual Disease Assessed by Multiparameter Flow Cytometry in Multiple Myeloma: Impact on Outcome in the Medical Research Council Myeloma IX Study." Journal of Clinical Oncology 31, no. 20 (2013): 2540–47. http://dx.doi.org/10.1200/jco.2012.46.2119.
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Purpose To investigate the prognostic value of minimal residual disease (MRD) assessment in patients with multiple myeloma treated in the MRC (Medical Research Council) Myeloma IX trial. Patients and Methods Multiparameter flow cytometry (MFC) was used to assess MRD after induction therapy (n = 378) and at day 100 after autologous stem-cell transplantation (ASCT; n = 397) in intensive-pathway patients and at the end of induction therapy in non–intensive-pathway patients (n = 245). Results In intensive-pathway patients, absence of MRD at day 100 after ASCT was highly predictive of a favorable outcome (PFS, P < .001; OS, P = .0183). This outcome advantage was demonstrable in patients with favorable and adverse cytogenetics (PFS, P = .014 and P < .001, respectively) and in patients achieving immunofixation-negative complete response (CR; PFS, P = .0068). The effect of maintenance thalidomide was assessed, with the shortest PFS demonstrable in those MRD-positive patients who did not receive maintenance and longest in those who were MRD negative and did receive thalidomide (P < .001). Further analysis demonstrated that 28% of MRD-positive patients who received maintenance thalidomide became MRD negative. MRD assessment after induction therapy in the non–intensive-pathway patients did not seem to be predictive of outcome (PFS, P = .1). Conclusion MRD assessment by MFC was predictive of overall outcome in patients with myeloma undergoing ASCT. This predictive value was seen in patients achieving conventional CR as well as patients with favorable and adverse cytogenetics. The effects of maintenance strategies can also be evaluated, and our data suggest that maintenance thalidomide can eradicate MRD in some patients.
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Toldo, Irene, Diego Cecchin, Stefano Sartori, et al. "Multimodal neuroimaging in a child with sporadic hemiplegic migraine: A contribution to understanding pathogenesis." Cephalalgia 31, no. 6 (2010): 751–56. http://dx.doi.org/10.1177/0333102410392068.
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Background: Hemiplegic migraine (HM) is a rare variety of migraine with aura, characterized by motor deficits during the aura, often beginning in childhood. The hemiplegic attacks can be severe and prolonged but the prognosis is usually good. Data on neuroimaging, including diffusion-weighted imaging (DWI) and spectroscopy, during prolonged attacks of HM are quite limited, particularly in children. Case: An eight-year-old female had a prolonged attack of sporadic HM characterized by right-sided hemiplegia, global aphasia, fever and impairment of consciousness. MRI nine hours after hemiplegia onset was negative, while the following MRI scans (days 4 and 11) documented a progressive increase in cortical swelling in the left hemisphere with mild hyperintensity on DWI and mild reduction of apparent diffusion coefficient values. Proton MRI spectroscopy (MRS) (day 15) showed a decrease in the N-acetylaspartate/creatine ratio in the left hemisphere. 99mTc-ECD single-photon emission tomography (SPET) (day 27) showed marked left hemispheric hypoperfusion. The patient recovered completely after 40 days and neuroimaging follow-up (MRI and SPET) after six months was normal. The patient carried a missense mutation of the ATP1A2 gene. Conclusion: Multimodal neuroimaging (MRI, DWI, MRS, SPET) in a prolonged HM attack supports evidence for a primary neuronal dysfunction.
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Veeturi, Sricharan S., Nandor K. Pinter, Andre Monteiro, et al. "An Image-Based Workflow for Objective Vessel Wall Enhancement Quantification in Intracranial Aneurysms." Diagnostics 11, no. 10 (2021): 1742. http://dx.doi.org/10.3390/diagnostics11101742.
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Background: VWE in contrast-enhanced magnetic resonance imaging (MRI) is a potential biomarker for the evaluation of IA. The common practice to identify IAs with VWE is mainly based on a visual inspection of MR images, which is subject to errors and inconsistencies. Here, we develop and validate a tool for the visualization, quantification and objective identification of regions with VWE. Methods: N = 41 3D T1-MRI and 3D TOF-MRA IA images from 38 patients were obtained and co-registered. A contrast-enhanced MRI was normalized by the enhancement intensity of the pituitary stalk and signal intensities were mapped onto the surface of IA models generated from segmented MRA. N = 30 IAs were used to identify the optimal signal intensity value to distinguish the enhancing and non-enhancing regions (marked by an experienced neuroradiologist). The remaining IAs (n = 11) were used to validate the threshold. We tested if the enhancement area ratio (EAR—ratio of the enhancing area to the IA surface-area) could identify high risk aneurysms as identified by the ISUIA clinical score. Results: A normalized intensity of 0.276 was the optimal threshold to delineate enhancing regions, with a validation accuracy of 81.7%. In comparing the overlap between the identified enhancement regions against those marked by the neuroradiologist, our method had a dice coefficient of 71.1%. An EAR of 23% was able to discriminate high-risk cases with an AUC of 0.7. Conclusions: We developed and validated a pipeline for the visualization and objective identification of VWE regions that could potentially help evaluation of IAs become more reliable and consistent.
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Böckle, David, Paula Tabares Gaviria, Xiang Zhou, et al. "Real-World Experience with Minimal Residual Disease Testing with Next Generation Flow Cytometry and Functional Imaging in Multiple Myeloma." Blood 136, Supplement 1 (2020): 17–18. http://dx.doi.org/10.1182/blood-2020-140772.
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Background: Minimal residual disease (MRD) diagnostics in multiple myeloma (MM) are gaining increasing importance to determine response depth beyond complete remission (CR) since novel agents have shown to induce high rates of deep clinical responses. Moreover, recent reports indicated combining functional imaging with next generation flow cytometry (NGF) could be beneficial in predicting clinical outcome. This applies in particular to the subset of patients suffering from relapsed/refractory multiple myeloma (RRMM) who tend to show a higher incidence of residual focal lesions despite serological response. Here, we report our institutions experience with implementing both functional imaging and NGF-guided MRD diagnostics in clinical practice. Methods: Our study included patients with newly diagnosed multiple myeloma (NDMM) and RRMM achieving VGPR, CR or sCR. Bone marrow aspirates were obtained for MRD-testing according to IMWG 2016 criteria. Samples were collected between July 2019 and July 2020 and analyzed with NGF (according to EuroFlowTM guidelines) at a sensitivity level of 10-5. Results were compared to functional imaging obtained with positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI). High-risk disease was defined as presence of deletion 17p, translocation (14;16) or (4;14). Results: We included 66 patients with NDMM (n=39) and RRMM (n=27) who achieved VGPR or better. In patients with RRMM the median number of treatment lines was 2 (range 2-11). Fifteen patients suffered from high-risk disease. Median age at NGF diagnostics was 64 years (range 31-83). Among patients achieving VGPR (n=27), CR (n=10) and sCR (n=29) seventeen (26%) were MRD-negative by NGF testing. CR or better was significantly associated NGF MRD-negativity (p=0.04). Notably, rates of NGF MRD-negativity were similar among patients with NDMM (28%) and RRMM (26%). Even some heavily pretreated patients who underwent ≥ 4 lines of therapy achieved MRD-negativity on NGF (2 of 9). Functional imaging was performed in 46 (70%) patients with DW-MRI (n=22) and PET (n=26). Median time between NGF and imaging assessment was 2 days (range 0-147). Combining results from imaging and NGF, 12 out of 46 (26%) patients were MRD-negative with both methods (neg/neg). Three patients displayed disease activity as measured with both, imaging and NGF (pos/pos). Twenty-nine of the remaining patients were MRD-positive only according to NGF (pos/neg), while two patients were positive on imaging only (neg/pos). More patients demonstrated combined MRD-negativity on NGF and imaging (neg/neg) in the NDMM setting than in RRMM (32% versus 19%). We also observed that 30% of the patients with high-risk genetics showed MRD-negativity on both imaging and NGF. Of note, none of the patients with very advanced disease (≥4 previous lines) was MRD-negative on both techniques. Conclusion In the clinical routine, MRD diagnostics could be used to tailor maintenance and consolidation approaches for patients achieving deep responses by traditional IMWG criteria. Our real-world experience highlights that MRD-negativity can be achieved in patients suffering from high-risk disease and also in late treatment lines, supporting its value as endpoint for clinical trials. However, our data also support MRD diagnostics to be combined with functional imaging at least in the RRMM setting to rule out residual focal lesions. Future studies using MRD for clinical decision-making are highly warranted. Disclosures Einsele: Takeda: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; GlaxoSmithKline: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau. Rasche:Celgene/BMS: Honoraria; GlaxoSmithKline: Honoraria; Oncopeptides: Honoraria; Skyline Dx: Research Funding; Janssen: Honoraria; Sanofi: Honoraria.
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Yan, Jiun-Lin, Chao Li, Natalie R. Boonzaier, et al. "Multimodal MRI characteristics of the glioblastoma infiltration beyond contrast enhancement." Therapeutic Advances in Neurological Disorders 12 (January 2019): 175628641984466. http://dx.doi.org/10.1177/1756286419844664.
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Our inability to identify the invasive margin of glioblastomas hampers attempts to achieve local control. Diffusion tensor imaging (DTI) has been implemented clinically to delineate the margin of the tumor infiltration, its derived anisotropic (q) values can extend beyond the contrast-enhanced area and correlates closely with the tumor. However, its correlation with tumor infiltration shown on multivoxel proton magnetic resonance spectroscopy1 (MRS) and perfusion magnetic resonance imaging (MRI) should be investigated. In this study, we aimed to show tissue characteristics of the q-defined peritumoral invasion on MRS and perfusion MRI. Patients with a primary glioblastoma were included ( n = 51). Four regions of interest were analyzed; the contrast-enhanced lesion, peritumoral abnormal q region, peritumoral normal q region, and contralateral normal-appearing white matter. MRS, including choline (Cho)/creatinine (Cr), Cho/N-acetyl-aspartate (NAA) and NAA/Cr ratios, and the relative cerebral blood volume (rCBV) were analyzed. Our results showed an increase in the Cho/NAA ( p = 0.0346) and Cho/Cr ( p = 0.0219) ratios in the peritumoral abnormal q region, suggestive of tumor invasion. The rCBV was marginally elevated ( p = 0.0798). Furthermore, the size of the abnormal q regions was correlated with survival; patients with larger abnormal q regions showed better progression-free survival (median 287 versus 53 days, p = 0.001) and overall survival (median 464 versus 274 days, p = 0.006) than those with smaller peritumoral abnormal q regions of interest. These results support how the DTI q abnormal area identifies tumor activity beyond the contrast-enhanced area, especially correlating with MRS.
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Gastaldi, Matteo, Enrico Marchioni, Paola Banfi, et al. "Predictors of outcome in a large retrospective cohort of patients with transverse myelitis." Multiple Sclerosis Journal 24, no. 13 (2017): 1743–52. http://dx.doi.org/10.1177/1352458517731911.
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Background: Transverse myelitis (TM) is an inflammatory disorder that can be idiopathic or associated with central nervous system autoimmune/dysimmune inflammatory diseases, connective tissue autoimmune diseases, or post-infectious neurological syndromes. Prognosis of initial TM presentations is uncertain. Objective: To identify outcome predictors in TM. Methods: Retrospective study on isolated TM at onset. Scores ⩾3 on the modified Rankin scale (mRS) marked high disability. Results: A total of 159 patients were identified. TM was classified as follows: idiopathic (I-TM, n = 53), post-infectious (PI-TM, n = 48), associated with multiple sclerosis (MS-TM, n = 51), or neuromyelitis optica spectrum disorders/connective tissue autoimmune diseases/neurosarcoidosis ( n = 7). At follow-up (median, 55 months; interquartile range, 32–80), 42 patients were severely disabled, and patients with I-TM or PI-TM showed the worst outcomes. Predictors of disability were infectious antecedents, sphincter and pyramidal symptoms, high mRS scores, blood–cerebrospinal fluid barrier damage, lumbar magnetic resonance imaging (MRI) lesions on univariate analysis, and older age (odds ratio (OR), 1.1; 95% confidence interval (CI), 1.0–1.1), overt/subclinical involvement of the peripheral nervous system (PNS) (OR, 9.4; 95% CI, 2.2–41.0), complete TM (OR, 10.8; 95% CI, 3.4–34.5) on multivariate analysis. Conclusion: Our findings help define prognosis and therapies in TM at onset. Infectious antecedents and PNS involvement associate with severe prognosis. Nerve conduction studies and lumbar MRI could improve the prognostic assessment of this condition.
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Strasser-Fuchs, S., C. Enzinger, S. Ropele, M. Wallner, and F. Fazekas. "Clinically benign multiple sclerosis despite large T2 lesion load: Can we explain this paradox?" Multiple Sclerosis Journal 14, no. 2 (2007): 205–11. http://dx.doi.org/10.1177/1352458507082354.
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Magnetic resonance imaging (MRI) techniques such as magnetization transfer imaging and magnetic resonance spectroscopy (MRS) may reveal otherwise undetectable tissue damage in multiple sclerosis (MS) and can serve to explain more severe disability than expected from conventional MRI. That an inverse situation may exist where non-conventional quantitative MRI and MRS metrics would indicate less abnormality than expected from T2 lesion load to explain preserved clinical functioning was hypothesized. Quantitative MRI and MRS were obtained in 13 consecutive patients with clinically benign MS (BMS; mean age 44 ± 9 years) despite large T 2 lesion load and in 15 patients with secondary progressive MS (SPMS; mean age 47 ± 6 years) matched for disease duration. The magnetization transfer ratio (MTR), magnetization transfer rate ( kfor), brain parenchymal fraction (BPF) and brain metabolite concentrations from proton MRS were determined. BMS patients were significantly less disabled than their SPMS counterparts (mean expanded disability status score: 2.1 ± 1.1 versus 6.2 ± 1.1; P < 0.001) and had an even somewhat higher mean T2 lesion load (41.2 ± 27.1 versus 27.9 ± 24.8 cm3; P = 0.19). Normal appearing brain tissue histogram metrics for MTR and kfor, mean MTR and kfor of MS lesions and mean BPF were similar in BMS and SPMS patients. Levels of N-acetyl-aspartate, choline and myoinositol were comparable between groups. This study thus failed to explain the preservation of function in our BMS patients with large T2 lesion load by a higher morphologic or metabolic integrity of the brain parenchyma. Functional compensation must come from other mechanisms such as brain plasticity. Multiple Sclerosis 2008; 14: 205—211. http://msj.sagepub.com
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Ben Hassen, Wagih, Nicolas Raynaud, Nicolas Bricout, et al. "MT-DRAGON score for outcome prediction in acute ischemic stroke treated by mechanical thrombectomy within 8 hours." Journal of NeuroInterventional Surgery 12, no. 3 (2019): 246–51. http://dx.doi.org/10.1136/neurintsurg-2019-015105.
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ObjectivesThe MRI-DRAGON score includes clinical and MRI parameters and demonstrates a high specificity in predicting 3 month outcome in patients with acute ischemic stroke (AIS) treated with intravenous tissue plasminogen activator (IV tPA). The aim of this study was to adapt this score to mechanical thrombectomy (MT) in a large multicenter cohort.MethodsConsecutive cases of AIS treated by MT between January 2015 and December 2017 from three stroke centers were reviewed (n=1077). We derived the MT-DRAGON score by keeping all variables of the MRI-DRAGON score (age, initial National Institutes of Health Stroke Scale score, glucose level, pre-stroke modified Rankin Scale (mRS) score, diffusion weighted imaging-Alberta Stroke Program Early CT score ≤5) and considering the following variables: time to groin puncture instead of onset to IV tPA time and occlusion site. Unfavorable 3 month outcome was defined as a mRS score >2. Score performance was evaluated by c statistics and an external validation was performed.ResultsAmong 679 included patients (derivation and validation cohorts, n=431 and 248, respectively), an unfavorable outcome was similar between the derivation (51.5%) and validation (58.1%, P=0.7) cohorts, and was significantly associated with all MT-DRAGON parameters in the multivariable analysis. The c statistics for unfavorable outcome prediction was 0.83 (95%CI 0.79 to 0.88) in the derivation and 0.8 (95%CI 0.75 to 0.86) in the validation cohort. All patients (n=55) with an MT-DRAGONscore ≥11 had an unfavorable outcome and 60/63 (95%) patients with an MT-DRAGON score ≤2 points had a favorable outcome.ConclusionThe MT-DRAGON score is a simple tool, combining admission clinical and radiological parameters that can reliably predict 3 month outcome after MT.
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Jamroz-Wiśniewska, Anna, Radosław Zajdel, Agnieszka Słowik, et al. "Modified Rio Score with Platform Therapy Predicts Treatment Success with Fingolimod and Natalizumab in Relapsing-Remitting Multiple Sclerosis Patients." Journal of Clinical Medicine 10, no. 9 (2021): 1830. http://dx.doi.org/10.3390/jcm10091830.
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Background: Reliable markers of disease outcomes in multiple sclerosis (MS) would help to predict the response to treatment in patients treated with high efficacy drugs. No evidence of disease activity (NEDA) has become a treatment goal whereas the modified Rio score (MRS) predicts future suboptimal responders to treatment. The aim of our study was to identify factors that would predict poor response to treatment with natalizumab and fingolimod. Methods: In the multicenter prospective trial, 336 subjects were enrolled, initiating therapy with natalizumab (n = 135) or fingolimod (n = 201). Data on relapse rate, the expanded disability status scale, and MRI results were collected, and MRS was estimated. Results: NEDA-3 after the first year of therapy was 73.9% for natalizumab and 54.8% for fingolimod (p < 0.0001). Patients with MRS = 0 in the last year on platform therapy had the best NEDA-3 (71%) and patients with MRS = 3 had the worst NEDA-3 (41%) in the first year of treatment with the second-line therapy. Conclusion: We conclude that switching to the second-line therapy should occur earlier to enable better results for patients treated with natalizumab or fingolimod. The outcome on both drugs is better with better neurological conditions and lower MRS of the patient on the platform therapy.
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Zhang, Zhongwei, Quanfei Meng, Ziping Li, Bitao Pan, Ravinder R. Regatte, and Mark E. Schweitzer. "Simultaneous Visualization of Nerves and Vessels of the Lower Extremities Using Magnetization-Prepared Susceptibility Weighted Magnetic Resonance Imaging at 3.0 T." Operative Neurosurgery 70, suppl_1 (2011): ons1—ons7. http://dx.doi.org/10.1227/neu.0b013e31822da57f.
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Abstract BACKGROUND: Identifying the extent of involvement of the vessel and nerve, particularly in regard to preoperative evaluation and precise localization of the tumor and its relation to the structures of the extremities, has important applications for advancing the treatment of lower extremity diseases. OBJECTIVE: To review the technical feasibility of simultaneous visualization of nerves and vessels of the lower extremities by using magnetization-prepared susceptibility-weighted magnetic resonance (MR) imaging (MP-SWI) at 3.0T. METHODS: Ten healthy volunteers and 10 patients were studied. Optimized MP-SWI, MR neurography (MRN) based on 3D diffusion-weighted steady-state free precession imaging and contrast-enhanced MR angiography (CE-MRA) sequences were performed for each subject. The means of signal-to-noise ratio (SNR)n, SNRv, SNRm, contrast-to-noise ratio (CNR)n,m and CNRv,m were calculated and the certainty of identifying nerves and vessels was determined. CNRn,m between MP-SWI and MRN, and CNRv,m between MP-SWI and CE-MRA were compared. RESULTS: MP-SWI provides slightly poorer CNRv,m than CE-MRA, whereas MP-SWI provides a better CNRn,m than MRN. In thin-slice-thickness maximum-intensity projection arbitrary planes, the sciatic nerve and its branches were clearly identified (score 1 or 2 of 2) in 17 subjects (85%); the femoral artery and the main branches were identified (score 1 or 2 of 2) in all 20 subjects (100%). The nerves are isointense to slightly hypointense to muscle, and the vessels show a more obvious hyperintense signal than muscle in MP-SWI. CONCLUSION: The proposed MP-SWI demonstrates the feasibility of simultaneously visualizing nerves and vessels of the lower extremities without using an exogenous contrast agent. It may enable straightforward localization of a disease process to a specific nerve and vessel.
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Chaumeil, Myriam M., Julien Valette, Céline Baligand, et al. "pH as a Biomarker of Neurodegeneration in Huntington's Disease: A Translational Rodent-Human MRS Study." Journal of Cerebral Blood Flow & Metabolism 32, no. 5 (2012): 771–79. http://dx.doi.org/10.1038/jcbfm.2012.15.
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Early diagnosis and follow-up of neurodegenerative diseases are often hampered by the lack of reliable biomarkers. Neuroimaging techniques like magnetic resonance spectroscopy (MRS) offer promising tools to detect biochemical alterations at early stages of degeneration. Intracellular pH, which can be measured noninvasively by 31P-MRS, has shown variations in several brain diseases. Our purpose has been to evaluate the potential of MRS-measured pH as a relevant biomarker of early degeneration in Huntington's disease (HD). We used a translational approach starting with a preclinical validation of our hypothesis before adapting the method to HD patients. 31P-MRS-derived cerebral pH was first measured in rodents during chronic intoxication with 3-nitropropionic acid (3NP). A significant pH increase was observed early into the intoxication protocol (pH = 7.17 ± 0.02 after 3 days) as compared with preintoxication (pH = 7.08 ± 0.03). Furthermore, pH changes correlated with the 3NP-induced inhibition of succinate dehydrogenase and preceded striatum lesions. Using a similar MRS approach implemented on a clinical MRI, we then showed that cerebral pH was significantly higher in HD patients ( n = 7) than in healthy controls ( n = 6) (7.05 ± 0.03 versus 7.02 ± 0.01, respectively, P = 0.026). Altogether, both preclinical and human data strongly argue in favor of MRS-measured pH being a promising biomarker for diagnosis and follow-up of HD.
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Munkeby, B. H., C. De Lange, K. E. Emblem, et al. "A piglet model for detection of hypoxic-ischemic brain injury with magnetic resonance imaging." Acta Radiologica 49, no. 9 (2008): 1049–57. http://dx.doi.org/10.1080/02841850802334224.
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Background: Early detection of hypoxic-ischemic (HI) injury in the asphyxic newborn is important because present prognostic factors are inadequate. Furthermore, therapeutic interventions may have additional benefit if initiated in time. Purpose: To assess whether the use of a combined protocol including conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), and proton MR spectroscopy (MRS) could detect pathological findings in a piglet model 7 hours after HI. Material and Methods: Ten piglets were submitted to HI for 30 min followed by reoxygenation with 21% O2 for 7 hours. MRI at 1.5T was done prior to and 7 hours after the HI. Single-voxel proton MRS was performed, and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in the basal ganglia. MRS identified N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac). Histology and microtubule-associated protein 2 (MAP-2) staining was performed in the basal ganglia at the end of the experiment. Results: Compared to baseline, ADC, NAA/Cho, and NAA/Cr were significantly reduced after 7 hours ( P<0.001, P=0.01, and P=0.05, respectively) and FA values were increased ( P<0.025). The ratios of Lac/Cho and Lac/NAA were significantly higher after 7 hours compared to baseline ( P<0.001). Presence of necrosis correlated well with reduced ADC ( RS=0.91) and presence of Lac ( RS=0.80). Histology and MAP-2 staining showed more than 90% necrosis in eight piglets, 60% in one piglet, and no necrosis in one piglet. Conclusion: Diffusion MRI and proton MRS can detect HI injury in the piglet brain 7 hours after hypoxia. DWI and MRS can be used to give useful prognostic information. This piglet model may potentially be used to mimic clinical situations and is suitable for further research investigating HI injury.
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Warren, K. E., D. Draper, and J. A. Butman. "Multiparametric magnetic resonance imaging (MRI) of diffuse intrinsic pontine gliomas (DIPG) after radiation therapy (XRT)." Journal of Clinical Oncology 24, no. 18_suppl (2006): 1579. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.1579.
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1579 Background: The diagnosis and treatment of DIPG are based on typical MRI findings because of the inherent risk of biopsy. The standard treatment for this tumor is XRT. The limited ability of standard MRI to distinguish tumor from treatment effect hampers the determination of tumor response and time to progression. The objective of this study is to measure biochemical and physiologic MRI markers in DIPG after XRT that may aid in assessment of response. Methods: Fifteen pediatric patients (5 y, range, 1.8–12) with DIPG involving >50% of the pons and treated with XRT only were evaluated 12–64 days (median 38) following XRT (50.4–67.2 Gy, median 54 Gy) by MRI at 1.5 T. Standard T1, T2, and FLAIR MRI was performed in all cases. In addition, proton MR spectroscopy (MRS) was performed in 10 cases, MRS imaging (1H-MRSI) in 12, dynamic contrast enhanced MRI (DCE-MRI) in 14, and dynamic susceptibility weighted MRI (DSC-MRI) in 9. Ktrans and rCBV were measured using ROIs on enhancing portions of the tumor from the DCE- and DSC-MRI data after kinetic modeling. Results: Tumor area changed following XRT by a median of −29% (range, −61 to +37; SD, 33) and −17% (range, −65 to +101; SD, 45) on T2 and FLAIR, respectively. Enhancement was identified in 15 of 15 patients following XRT, and in only 6 of 15 prior to XRT (P = 0.0039 McNemar’s test). Following XRT, Choline: N-Acetyl Aspartate (CHO:NAA) ratio was 3.2 ± 1.9 by single voxel MRS, and the “worst voxel” CHO:NAA ratio was 3.5 ± 1.5 by 1H-MRSI. Overall, rCBV (1.98 ± 1.30) was elevated relative to normal cerebellum. However in 4 of these cases, rCBV was markedly elevated (>2), 4 were normal (1.0–1.3), and one was markedly reduced (0.6).Similarly, disruption of the blood-tumor barrier was variable across the group. Ktrans, a measure of permeability, ranged from 0.000 to 0.026 s−1, averaging 0.0086 ± 0.0085 s−1. Conclusions: Although all patients had a structurally similar tumor on MRI prior to XRT, significant variability in physiologic and metabolic response to XRT as measured by multiparametric MRI are noted. Presumably this variability represents real biologic differences resulting from differential responses to therapy. Determination of the prognostic significance is ongoing. No significant financial relationships to disclose.
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Schlenz, Alyssa M., Michael U. Antonucci, Rebecca Cafiero, Nina-Serena Burkett, and Julie Kanter. "Moyamoya Disease Predicts Progression of Cerebral Vasculopathy in Patients with Sickle Cell Disease Despite Chronic Transfusion Therapy." Blood 126, no. 23 (2015): 2071. http://dx.doi.org/10.1182/blood.v126.23.2071.2071.
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Abstract Introduction: Patients with sickle cell disease (SCD) develop multi-organ complications due to hemolysis, inflammation, and vascular occlusion that results in small vessel obstruction throughout the body. In the brain, however, large cerebral vessels are also damaged resulting in occlusion or stenosis and subsequent development of abnormal collateral vasculature and moyamoya disease. Chronic red cell transfusion (CRCT) therapy significantly reduces the risk of stroke in children with abnormal transcranial doppler (TCD) studies and is also effective in reducing stroke recurrence in those with a history of overt or silent stroke; however, it is unclear if CRCT halts or reverses the progression of vasculopathy. The present study evaluated cerebrovascular stenosis and moya moya disease as risk factors for progression of vasculopathy over time in a cohort of patients with SCD who were started on CRCT therapy as children for stroke prevention. Methods: A retrospective cohort study (with IRB approval) was used to evaluate cerebrovascular changes in patients on CRCT.Patients were included in the study if they had received CRCT for stroke prevention for at least 12 months and had at least two serial magnetic resonance imaging and angiography (MRI/MRA) studies for review. For the imaging analysis, the patient's MRI/MRA closest to the initiation of CRCT (i.e. baseline imaging) was compared to the most recent imaging available by a neuro radiologist who was blind to the patient's clinical history. Additional demographic information included the patient's current age, gender, indication for CRCT, years on CRCT, and laboratory results for pre-transfusion % hemoglobin S (HbS). Results: Forty patients with SCD (current age: M = 16.48, SD = 5.10; 23 male, 17 female) were included. Average duration of CRCT therapy was 9.96 years (SD = 5.67) and average pre-transfusion HbS levels were 42.52% (SD = 9.88). Patients were initiated on therapy due to: overt stroke (n = 19), silent stroke (n = 2), and abnormal TCD (n = 20). Of the 20 patients initiated on therapy due to abnormal TCD, 7 were found to have abnormal MRI at baseline consistent with silent stroke. One of these patients was also found to have co-occurring moyamoya disease, despite no evidence of prior overt stroke. At baseline, 45% (n = 18) of patients had abnormal MRA and 25% (n = 10) had moyamoya disease. Progression of vasculopathy occurred in 15% (n = 6) of patients, all of whom had a history of moya moya disease at baseline (5 patients with overt stroke and 1 with silent stroke). Of the remaining 3 patients with moya moya disease at baseline, 2 remained stable with no improvement and 1 demonstrated improvement on MRA. For patients with abnormal MRA, but no history of moya moya disease (n = 9), 5 demonstrated improvement (2 patients with silent stroke and 3 with overt stroke). Conclusions: Progression of vasculopathy was common among patients with baseline moyamoya disease despite CRCT. Also notable, however, was improvement in vasculopathy (as defined by reduction of stenosis) in 6 patients, the majority of whom had not developed moyamoya prior to the initiation of CRCT suggesting that more mild vasculopathy can be reversed with early intervention. Patients with moya moya disease warrant ongoing annual assessment as they may require vascular bypass to prevent further worsening. Future large, multi-site investigations are needed to identify improved biomarkers and further understand characteristics of patients who demonstrate improvement versus progression of vasculopathy on CRCT. Disclosures No relevant conflicts of interest to declare.
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Bourcier, Romain, Wagih Ben Hassen, Sébastien Soize, et al. "Susceptibility vessel sign on MRI predicts better clinical outcome in patients with anterior circulation acute stroke treated with stent retriever as first-line strategy." Journal of NeuroInterventional Surgery 11, no. 4 (2018): 328–33. http://dx.doi.org/10.1136/neurintsurg-2018-014217.
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BackgroundSusceptibility vessel sign (SVS) can be a useful MRI biomarker of an occlusion but its relationship with clinical outcomes of acute ischemic stroke (AIS) is yet to be fully elucidated.ObjectiveTo investigate SVS in relation to the clinical outcomes after mechanical thrombectomy using a stent retriever (SR) as first-line approach in patients with AIS.Material and methodsWe included patients with a first-line SR approach for anterior AIS from the the Contact Aspiration vs Stent Retriever for Successful Revascularization (ASTER) and THRombectomie des Artères CErebrales (THRACE) trials when both baseline imaging of SVS and 90-day modified Rankin Scale (mRS) scores were available. Patients were assigned to two groups based on the presence of an SVS (independent core laboratory), and the overall distributions of the mRS score at 90 days (shift analysis) and clinical independence (mRS score ≤2) were compared.Results217 patients were included and SVS was diagnosed in 76.0% of cases (n=165, 95% CI 70.4% to 81.7%). After adjustment for potential confounders, SVS+ was significantly associated with 90-day mRS improvement (adjusted common OR=2.75; 95% CI 1.44 to 5.26) and favorable outcome (adjusted common OR=2.76; 95% CI 1.18 to 6.45).ConclusionBased on results for patients of the ASTER and THRACE trials receiving first-line SR treatment, SVS was associated with lower disability at 3 months. Large prospective studies using MRI-based thrombus evaluation are warranted.
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Claes, Stephan, Philippe Volcke, Koenraad Devriendt, et al. "Regional localization of a gene for nonspecific XLMR to Xp11.3-p11.23 (MRX51) and tentative localization of an MRX gene to Xq23-q26.1." American Journal of Medical Genetics 85, no. 3 (1999): 283–87. http://dx.doi.org/10.1002/(sici)1096-8628(19990730)85:3<283::aid-ajmg19>3.0.co;2-n.
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Köhnke, Thomas, Sandra Rechkemmer, Veit Leonhard Bücklein, et al. "Improved Detection of Minimal Residual Disease By Flow Cytometry in AML By Combining Manual Gating and Visne Clustering." Blood 126, no. 23 (2015): 2593. http://dx.doi.org/10.1182/blood.v126.23.2593.2593.
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Abstract Background: In acute myeloid leukemia (AML), detection of minimal residual disease (MRD) by flow cytometry is an adverse prognostic factor besides pre-treatment risk classifications, including cytogenetic and molecular aberrations. High dimensional multiparameter flow cytometry (MPFC) offers improved sensitivity and specificity, however manual analysis is increasingly challenging. In this study, we explore the value of the recently proposed viSNE algorithm to quantify MRD levels in patients with AML achieving complete remission (CR) after intensive induction chemotherapy. Methods: Bone marrow samples from patients with AML (excluding patients with acute promyelocytic leukemia) were analyzed by 8-10 MPFC using a NAVIOS flow cytometer (Beckman Coulter, Brea, CA, USA). Only patients achieving a CR or CR with incomplete blood count recovery (CRi) post-induction were included in this analysis. Manual gating of MRD flow data was performed as described previously (Köhnke et al., Leukemia 2014) using a cutoff for MRD positivity of 0.1%. The viSNE algorithm was performed as described previously (Amir et al., Nat. Biotech. 2013) and MRD positivity was defined as the presence of a distinct cluster of >100 cells which consisted of >90% patient cells. Kaplan-Meier estimator and log-rank test as well as Cox's proportional hazards regression model were used to analyze survival data. Results: Post-induction flow cytometry and clinical data of 38 patients with AML achieving CR (n=34) or CRi (n=4) were available for analysis (median age 53 years; de-novo AML n=32, tAML n=1, sAML n=5). Most patients belonged to the intermediate cytogenetic risk group (MRC favorable n=5, intermediate n=22, adverse n=11). 19/38 patients were MRD positive post-induction by manual gating. 12/19 patients deemed MRD positive relapsed, whereas 3/19 patients deemed MRD negative relapsed. Therefore, MRD positivity by manual gating correlated with reduced relapse free survival (median RFS for MRD positive patients: 7.5 months vs. median not reached for MRD negative patients, log-rank test p=0.017). For overall survival (OS), no significant impact of MRD positivity could be detected so far (p=0.3), however follow-up was short (median follow-up 9.3 months). MRD positivity by manual gating remained an independent risk factor for RFS (HR 4.8, p=0.021) when compared to genetic risk and age. MRD positivity by viSNE clustering was seen in 19/38 patients. 10/19 patients deemed MRD positive by viSNE relapsed, while 5/19 deemed MRD negative by viSNE experienced a relapse. This resulted in a trend towards shorter RFS for MRD positivity by viSNE (median RFS 9.9 months vs. 19.0 months for MRD negative patients, p=0.185). Among the patients deemed MRD positive by viSNE who did not relapse, i.e. false-positive patients, follow-up was very short (<3.5 months) in 4/9 cases and final judgment whether these patients are truly negative should be withheld. However, differentiation between healthy monocytes and potential MRD cells by viSNE seems to be especially challenging and warrants optimization. Nevertheless, within the group of patients deemed MRD negative by manual gating, viSNE was able to detect all patients who experienced a subsequent relapse. To maximize sensitivity for MRD detection, we therefore combined the results of both methods and defined MRD positivity as positivity by manual gating and/or viSNE clustering. Using this combined strategy, 28/38 patients were defined as MRD positive and 10/38 as MRD negative. Within the MRD positive group, 15/28 patients relapsed, whereas none of the patients in the MRD negative group relapsed (Figure 1, median RFS for MRD positive patients: 7.7 months, log-rank test p=0.028). Of note, within the MRD negative group only 2 patients (both with intermediate genetic risk) went on to receive a allogeneic stem cell transplantation whereas 8 remained in remission with chemotherapy alone. Conclusion: In summary, viSNE clustering used in combination with manual gating improves the sensitivity of MRD detection by flow cytometry. Importantly, viSNE is able to detect MRD positivity within the manual MRD negative patient population. This is the first report of MRD detection in AML using this method. However, improvements in the algorithm as well as further studies are needed to validate the prognostic value of viSNE clustering in AML. Disclosures No relevant conflicts of interest to declare.
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Yamasaki, Fumiyuki, Takeshi Takayasu, Ryo Nosaka, et al. "Magnetic resonance spectroscopy detection of high lipid levels in intraaxial tumors without central necrosis: a characteristic of malignant lymphoma." Journal of Neurosurgery 122, no. 6 (2015): 1370–79. http://dx.doi.org/10.3171/2014.9.jns14106.
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OBJECT The differentiation of malignant lymphomas from gliomas or malignant gliomas by conventional MRI can be difficult. The authors studied Gd-enhanced MR images to obtain a differential diagnosis between malignant lymphomas and gliomas without central necrosis or cystic changes and investigated the diagnostic value of single-voxel proton MR spectroscopy (1H-MRS) using different parameters, including lipid levels. METHODS This was a retrospective study of patients with primary malignant CNS lymphoma (n = 17) and glioma (n = 122 [Grades I, II, III, and IV in 10, 30, 33, and 49 patients, respectively]) who were treated between 2007 and 2013. The authors focused on 15 patients with homogeneously enhanced primary malignant CNS lymphomas and 7 homogeneously enhanced gliomas. Images of all the included tumors were acquired with 1H-MRS at 3 T, and the diagnoses were histologically confirmed. RESULTS Using a short echo time 1H-MRS, large lipid peaks were observed in all 17 patients with a malignant lymphoma, in 39 patients (79.6%) with a Grade IV glioma, and in 10 patients (30.3%) with a Grade III glioma. A focus on homogeneously enhanced tumors revealed large lipid peaks in 15 malignant lymphomas that were free of central necrosis on Gd-enhanced T1-weighted images. Conversely, in the 7 homogeneously enhanced gliomas (glioblastoma and anaplastic astrocytoma, n = 2 each; anaplastic oligodendroglioma, diffuse astrocytoma, and pilomyxoid astrocytoma, n = 1 each), lipid peaks were small or absent. CONCLUSIONS Large lipid peaks on 1H-MRS images of tumors without central necrosis were characteristic of malignant lymphomas. Conversely, small or absent lipid peaks in intraaxial tumors without central necrosis were strongly suggestive of glioma.
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Nguyen, Do Dung, and Qingchun Chen. "On the Energy Efficient Multiple Pair Communications in Two-Way Massive MIMO Relaying Networks with Imperfect CSI." Journal of Science and Technology: Issue on Information and Communications Technology 3, no. 1 (2017): 9. http://dx.doi.org/10.31130/jst.2017.33.
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Multiple-pair two-way communication in massive multiple-input multiple-output (MIMO) relay network is studied in this article wherein K single antenna source nodes exchange their messages to the corresponding K single antenna destination nodes with the help of one relay provisioned with N(N >> K) antenna array. And the energy efficient two-way multiple-pair communication in Massive MIMO relay network through the precoding design at relay is addressed. It is shown hat, even with the imperfect channel state information at the relay, the maximum ratio combining-maximum ratio transmission (MRC/MRT) precoding and the zero-forcing reception zero-forcing transmission (ZFR/ZFT) precoding at relay can be employed to mitigate inter-pair interference. The asymptotic signal to interference plus noise ratio (SINR) analysis of four power-scaling schemes in the regime of very large number of antenna at relay shows that, the inter-pair interference can be eliminated, the effect of the small-scale fading can be averaged out; the total transmit power consumption can be reduced for a better energy efficient multiple-pair communication when the number of antenna at relay is large enough. Moreover, when the transmit power at relay is sufficient, both the MRC/MRT and the ZFR/ZFT based relaying strategy can effectively cope with the channel state information (CSI) error. Simulation results are presented to validate our analysis.