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1

A.G. Teixeira, Rui Pedro, Shaihan J. Malik, and Joseph V. Hajnal. "Fast quantitative MRI using controlled saturation magnetization transfer." Magnetic Resonance in Medicine 81, no. 2 (September 14, 2018): 907–20. http://dx.doi.org/10.1002/mrm.27442.

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2

Cercignani, Mara, and Daniel C. Alexander. "Optimal acquisition schemes for in vivo quantitative magnetization transfer MRI." Magnetic Resonance in Medicine 56, no. 4 (August 10, 2006): 803–10. http://dx.doi.org/10.1002/mrm.21003.

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3

Rovaris, Marco, Elda Judica, Jaume Sastre-Garriga, Alex Rovira, Maria Pia Sormani, Beatrice Benedetti, Tijmen Korteweg, et al. "Large-scale, multicentre, quantitative MRI study of brain and cord damage in primary progressive multiple sclerosis." Multiple Sclerosis Journal 14, no. 4 (January 21, 2008): 455–64. http://dx.doi.org/10.1177/1352458507085129.

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Although the mechanisms underlying the accumulation of disability in primary progressive (PP) multiple sclerosis (MS) are still unclear, a major role seems to be played by `occult' tissue damage. We investigated whether conventional and magnetization transfer (MT) MRI may provide complementary information for the assessment of PPMS severity. Conventional and MT MRI scans from 226 PPMS patients and 84 healthy controls were collected for centralized analysis. The expanded disability status scale (EDSS) score was rated at the time of MRI acquisition. T2 lesion volume, normalized brain volume (NBV) and cervical cord cross-sectional area (CSA) were measured. Magnetization transfer ratio (MTR) histograms from whole brain tissue, normal-appearing white matter and grey matter (NAGM) were also obtained. Mean NBV, CSA and MTR histogram-derived metrics showed significant inter-centre heterogeneity. After correcting for the acquisition centre, pooled average MTR and histogram peak height values were different between PPMS patients and controls for all tissue classes ( P-values between 0.03 and 0.0001). More severe brain and cord atrophy and MT MRI-detectable NAGM damage were found in patients who required walking aids than in those who did not ( P-values: 0.03, 0.001 and 0.016). A composite score of NBV, CSA, whole brain and NAGM MTR histogram peak height z-scores was correlated with patients' EDSS ( r = 0.37, P 0.001). Magnetization transfer MRI might provide information complementary to that given by conventional MRI when assessing PPMS severity. Sequence-related variability of measurements makes the standardization of MT MRI acquisition essential for the design of multicentre studies. Multiple Sclerosis 2008; 14: 455—464. http://msj.sagepub.com
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4

Sled, John G., and G. Bruce Pike. "Quantitative Interpretation of Magnetization Transfer in Spoiled Gradient Echo MRI Sequences." Journal of Magnetic Resonance 145, no. 1 (July 2000): 24–36. http://dx.doi.org/10.1006/jmre.2000.2059.

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5

Li, Weiguo, Zhuoli Zhang, Jodi Nicolai, Guang-Yu Yang, Reed A. Omary, and Andrew C. Larson. "Quantitative magnetization transfer MRI of desmoplasia in pancreatic ductal adenocarcinoma xenografts." NMR in Biomedicine 26, no. 12 (August 12, 2013): 1688–95. http://dx.doi.org/10.1002/nbm.3004.

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Alcaide-Leon, Paula, Kateryna Cybulsky, Stephanie Sankar, Courtney Casserly, General Leung, Marika Hohol, Daniel Selchen, Xavier Montalban, Aditya Bharatha, and Jiwon Oh. "Quantitative spinal cord MRI in radiologically isolated syndrome." Neurology - Neuroimmunology Neuroinflammation 5, no. 2 (January 18, 2018): e436. http://dx.doi.org/10.1212/nxi.0000000000000436.

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ObjectivesTo assess whether quantitative spinal cord MRI (SC-MRI) measures, including atrophy, and diffusion tensor imaging (DTI) and magnetization transfer imaging metrics were different in radiologically isolated syndrome (RIS) vs healthy controls (HCs).MethodsTwenty-four participants with RIS and 14 HCs underwent cervical SC-MRI on a 3T magnet. Manually segmented regions of interest circumscribing the spinal cord cross-sectional area (SC-CSA) between C3 and C4 were used to extract SC-CSA, fractional anisotropy, mean, perpendicular, and parallel diffusivity (MD, λ⊥, and λ||) and magnetization transfer ratio (MTR). Spinal cord (SC) lesions, SC gray matter (GM), and SC white matter (WM) areas were also manually segmented. Multivariable linear regression was performed to evaluate differences in SC-MRI measures in RIS vs HCs, while controlling for age and sex.ResultsIn this cross-sectional study of participants with RIS, 71% had lesions in the cervical SC. Of quantitative SC-MRI metrics, spinal cord MTR showed a trend toward being lower in RIS vs HCs (p = 0.06), and there was already evidence of brain atrophy (p = 0.05). There were no significant differences in SC-DTI metrics, GM, WM, or CSA between RIS and HCs.ConclusionThe SC demonstrates minimal microstructural changes suggestive of demyelination and inflammation in RIS. These findings are in contrast to established MS and raise the possibility that the SC may play an important role in triggering clinical symptomatology in MS. Prospective follow-up of this cohort will provide additional insights into the role the SC plays in the complex sequence of events related to MS disease initiation and progression.
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Adler, J., P. Schmiedlin-Ren, P. Higgins, T. Verrot, and E. Zimmermann. "Magnetization transfer MRI for quantitative assessment of intestinal fibrosis in Crohnʼs disease." Inflammatory Bowel Diseases 13, supplement (May 2007): 648–49. http://dx.doi.org/10.1097/00054725-200705001-00020.

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8

Adler, J., P. Schmiedlin-Ren, P. Higgins, T. Verrot, and E. Zimmermann. "Magnetization transfer MRI for quantitative assessment of intestinal fibrosis in Crohnʼs disease." Inflammatory Bowel Diseases 13 (May 2007): 648. http://dx.doi.org/10.1097/00054725-200705005-00020.

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9

Smith, Alex K., Richard D. Dortch, Lindsey M. Dethrage, and Seth A. Smith. "Rapid, high-resolution quantitative magnetization transfer MRI of the human spinal cord." NeuroImage 95 (July 2014): 106–16. http://dx.doi.org/10.1016/j.neuroimage.2014.03.005.

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10

Fatemi, Ali, Mary Ann Wilson, Andre W. Phillips, Michael T. McMahon, Jiangyang Zhang, Seth A. Smith, Edwin J. Arauz, et al. "In vivo Magnetization Transfer MRI Shows Dysmyelination in an Ischemic Mouse Model of Periventricular Leukomalacia." Journal of Cerebral Blood Flow & Metabolism 31, no. 10 (May 4, 2011): 2009–18. http://dx.doi.org/10.1038/jcbfm.2011.68.

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Periventricular leukomalacia, PVL, is the leading cause of cerebral palsy in prematurely born infants, and therefore more effective interventions are required. The objective of this study was to develop an ischemic injury model of PVL in mice and to determine the feasibility of in vivo magnetization transfer (MT) magnetic resonance imaging (MRI) as a potential monitoring tool for the evaluation of disease severity and experimental therapeutics. Neonatal CD-1 mice underwent unilateral carotid artery ligation on postnatal day 5 (P5); at P60, in vivo T2-weighted (T2w) and MT-MRI were performed and correlated with postmortem histopathology. In vivo T2w MRI showed thinning of the right corpus callosum, but no significant changes in hippocampal and hemispheric volumes. Magnetization transfer MRI revealed significant white matter abnormalities in the bilateral corpus callosum and internal capsule. These quantitative MT-MRI changes correlated highly with postmortem findings of reduced myelin basic protein in bilateral white matter tracts. Ventriculomegaly and persistent astrogliosis were observed on the ligated side, along with evidence of axonopathy and fewer oligodendrocytes in the corpus callosum. We present an ischemia-induced mouse model of PVL, which has pathologic abnormalities resembling autopsy reports in infants with PVL. We further validate in vivo MRI techniques as quantitative monitoring tools that highly correlate with postmortem histopathology.
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Granziera, Cristina, Jens Wuerfel, Frederik Barkhof, Massimiliano Calabrese, Nicola De Stefano, Christian Enzinger, Nikos Evangelou, et al. "Quantitative magnetic resonance imaging towards clinical application in multiple sclerosis." Brain 144, no. 5 (May 1, 2021): 1296–311. http://dx.doi.org/10.1093/brain/awab029.

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Abstract Quantitative MRI provides biophysical measures of the microstructural integrity of the CNS, which can be compared across CNS regions, patients, and centres. In patients with multiple sclerosis, quantitative MRI techniques such as relaxometry, myelin imaging, magnetization transfer, diffusion MRI, quantitative susceptibility mapping, and perfusion MRI, complement conventional MRI techniques by providing insight into disease mechanisms. These include: (i) presence and extent of diffuse damage in CNS tissue outside lesions (normal-appearing tissue); (ii) heterogeneity of damage and repair in focal lesions; and (iii) specific damage to CNS tissue components. This review summarizes recent technical advances in quantitative MRI, existing pathological validation of quantitative MRI techniques, and emerging applications of quantitative MRI to patients with multiple sclerosis in both research and clinical settings. The current level of clinical maturity of each quantitative MRI technique, especially regarding its integration into clinical routine, is discussed. We aim to provide a better understanding of how quantitative MRI may help clinical practice by improving stratification of patients with multiple sclerosis, and assessment of disease progression, and evaluation of treatment response.
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Wang, Feng, Daisuke Katagiri, Ke Li, Keiko Takahashi, Suwan Wang, Shinya Nagasaka, Hua Li, et al. "Assessment of renal fibrosis in murine diabetic nephropathy using quantitative magnetization transfer MRI." Magnetic Resonance in Medicine 80, no. 6 (May 30, 2018): 2655–69. http://dx.doi.org/10.1002/mrm.27231.

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13

Sled, John G., and G. Bruce Pike. "Quantitative imaging of magnetization transfer exchange and relaxation properties in vivo using MRI." Magnetic Resonance in Medicine 46, no. 5 (2001): 923–31. http://dx.doi.org/10.1002/mrm.1278.

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14

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 (October 17, 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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15

Jiang, Quan, James R. Ewing, Guang Liang Ding, Li Zhang, Zheng Gang Zhang, Lian Li, Polly Whitton, et al. "Quantitative Evaluation of BBB Permeability after Embolic Stroke in Rat Using MRI." Journal of Cerebral Blood Flow & Metabolism 25, no. 5 (February 16, 2005): 583–92. http://dx.doi.org/10.1038/sj.jcbfm.9600053.

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We sought to identify magnetic resonance imaging (MRI) parameters that can identify as well as predict disruption of the blood–brain barrier (BBB) after embolic stroke in the rat. Rats subjected to embolic stroke with ( n=13) and without ( n=13) rt-PA treatment were followed with MRI using quantitative permeability-related parameters, consisting of: transfer constant ( K i) of Gd- DTPA, the distribution volume ( Vp) of the mobile protons, and the inverse of the apparent forward transfer rate for magnetization transfer ( kinv), as well as the apparent diffusion coefficient of water ( ADCw), T2, and cerebral cerebral blood flow (CBF). Tissue progressing to fibrin leakage resulting from BBB disruption and adjacent tissue were then analyzed to identify MRI markers that characterize BBB disruption. Animals were killed after final MRI measurements at 24 h after induction of embolic stroke and cerebral tissues were perfused and stained to detect fibrin leakage. K i, Vp, and kinv were the most sensitive early (2 to 3 h) indices of the cerebral tissue that progresses to fibrin leakage. Cerebral blood flow was not significantly different between ischemic tissue with a compromised and an intact BBB. Our data indicate that compromise of the BBB can be sensitively predicted using a select set of MR parameters.
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16

Sinclair, C. D. J., R. S. Samson, D. L. Thomas, N. Weiskopf, A. Lutti, J. S. Thornton, and X. Golay. "P87 Quantitative magnetization transfer MRI: a potential new source of biomarkers in skeletal muscle?" Neuromuscular Disorders 20 (March 2010): S28—S29. http://dx.doi.org/10.1016/s0960-8966(10)70102-4.

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17

Bagnato, Francesca, Giulia Franco, Fei Ye, Run Fan, Patricia Commiskey, Seth A. Smith, Junzhong Xu, and Richard Dortch. "Selective inversion recovery quantitative magnetization transfer imaging: Toward a 3 T clinical application in multiple sclerosis." Multiple Sclerosis Journal 26, no. 4 (March 25, 2019): 457–67. http://dx.doi.org/10.1177/1352458519833018.

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Background:Assessing the degree of myelin injury in patients with multiple sclerosis (MS) is challenging due to the lack of magnetic resonance imaging (MRI) methods specific to myelin quantity. By measuring distinct tissue parameters from a two-pool model of the magnetization transfer (MT) effect, quantitative magnetization transfer (qMT) may yield these indices. However, due to long scan times, qMT has not been translated clinically.Objectives:We aim to assess the clinical feasibility of a recently optimized selective inversion recovery (SIR) qMT and to test the hypothesis that SIR-qMT-derived metrics are informative of radiological and clinical disease-related changes in MS.Methods:A total of 18 MS patients and 9 age- and sex-matched healthy controls (HCs) underwent a 3.0 Tesla (3 T) brain MRI, including clinical scans and an optimized SIR-qMT protocol. Four subjects were re-scanned at a 2-week interval to determine inter-scan variability.Results:SIR-qMT measures differed between lesional and non-lesional tissue ( p < 0.0001) and between normal-appearing white matter (NAWM) of patients with more advanced disability and normal white matter (WM) of HCs ( p < 0.05). SIR-qMT measures were associated with lesion volumes, disease duration, and disability scores ( p ⩽ 0.002).Conclusion:SIR-qMT at 3 T is clinically feasible and predicts both radiological and clinical disease severity in MS.
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Huang, Xunan, Ryan N. Schurr, Shuzhen Wang, Qiguang Miao, Tanping Li, and Guang Jia. "Development of Radiofrequency Saturation Amplitude-independent Quantitative Markers for Magnetization Transfer MRI of Prostate Cancer." Current Medical Imaging Formerly Current Medical Imaging Reviews 16, no. 6 (July 27, 2020): 695–702. http://dx.doi.org/10.2174/1573405615666190318153328.

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Background: In the United States, prostate cancer has a relatively large impact on men's health. Magnetic resonance imaging (MRI) is useful for the diagnosis and treatment of prostate cancer. Introduction: The purpose of this study was to develop a quantitative marker for use in prostate cancer magnetization transfer (MT) magnetic resonance imaging (MRI) studies that is independent of radiofrequency (RF) saturation amplitude. Methods: Eighteen patients with biopsy-proven prostate cancer were enrolled in this study. MTMRI images were acquired using four RF saturation amplitudes at 33 frequency offsets. ROIs were delineated for the peripheral zone (PZ), central gland (CG), and tumor. Z-spectral data were collected in each region and fit to a three-parameter equation. The three parameters are: the magnitude of the bulk water pool (Aw), the full width at half maximum of the water pool (Gw), and the magnitude of the bound pool (Ab), while, the slopes from the linear regressions of Gw and Ab on RF saturation amplitude (called kAb and kGw) were used as quantitative markers. Results: A pairwise statistically significant difference was found between the PZ and tumor regions for the two saturation amplitude-independent quantitative markers. No pairwise statistically significant differences were found between the CG and tumor regions for any quantitative markers. Conclusion: The significant differences between the values of the two RF saturation amplitudeindependent quantitative markers in the PZ and tumor regions reveal that these markers may be capable of distinguishing healthy PZ tissue from prostate cancer.
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Fritz, Nora E., Erin M. Edwards, Jennifer Keller, Ani Eloyan, Peter A. Calabresi, and Kathleen M. Zackowski. "Combining Magnetization Transfer Ratio MRI and Quantitative Measures of Walking Improves the Identification of Fallers in MS." Brain Sciences 10, no. 11 (November 6, 2020): 822. http://dx.doi.org/10.3390/brainsci10110822.

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Multiple sclerosis (MS) impacts balance and walking function, resulting in accidental falls. History of falls and clinical assessment are commonly used for fall prediction, yet these measures have limited predictive validity. Falls are multifactorial; consideration of disease-specific pathology may be critical for improving fall prediction in MS. The objective of this study was to examine the predictive value of clinical measures (i.e., walking, strength, sensation) and corticospinal tract (CST) MRI measures, both discretely and combined, to fall status in MS. Twenty-nine individuals with relapsing-remitting MS (mean ± SD age: 48.7 ± 11.5 years; 17 females; Expanded Disability Status Scale (EDSS): 4.0 (range 1–6.5); symptom duration: 11.9 ± 8.7 years; 14 fallers) participated in a 3T brain MRI including diffusion tensor imaging and magnetization transfer ratio (MTR) and clinical tests of walking, strength, sensation and falls history. Clinical measures of walking were significantly associated with CST fractional anisotropy and MTR. A model including CST MTR, walk velocity and vibration sensation explained >31% of the variance in fall status (R2 = 0.3181) and accurately distinguished 73.8% fallers, which was superior to stand-alone models that included only MRI or clinical measures. This study advances the field by combining clinical and MRI measures to improve fall prediction accuracy in MS.
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Orzyłowska, Anna, and Wendy Oakden. "Saturation Transfer MRI for Detection of Metabolic and Microstructural Impairments Underlying Neurodegeneration in Alzheimer’s Disease." Brain Sciences 12, no. 1 (December 30, 2021): 53. http://dx.doi.org/10.3390/brainsci12010053.

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Alzheimer’s disease (AD) is one of the most common causes of dementia and difficult to study as the pool of subjects is highly heterogeneous. Saturation transfer (ST) magnetic resonance imaging (MRI) methods are quantitative modalities with potential for non-invasive identification and tracking of various aspects of AD pathology. In this review we cover ST-MRI studies in both humans and animal models of AD over the past 20 years. A number of magnetization transfer (MT) studies have shown promising results in human brain. Increased computing power enables more quantitative MT studies, while access to higher magnetic fields improves the specificity of chemical exchange saturation transfer (CEST) techniques. While much work remains to be done, results so far are very encouraging. MT is sensitive to patterns of AD-related pathological changes, improving differential diagnosis, and CEST is sensitive to particular pathological processes which could greatly assist in the development and monitoring of therapeutic treatments of this currently incurable disease.
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McVicar, Nevin, Alex X. Li, Daniela F. Gonçalves, Miranda Bellyou, Susan O. Meakin, Marco AM Prado, and Robert Bartha. "Quantitative Tissue Ph Measurement during Cerebral Ischemia Using Amine and Amide Concentration-Independent Detection (AACID) with MRI." Journal of Cerebral Blood Flow & Metabolism 34, no. 4 (February 5, 2014): 690–98. http://dx.doi.org/10.1038/jcbfm.2014.12.

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Tissue pH is an indicator of altered cellular metabolism in diseases including stroke and cancer. Ischemic tissue often becomes acidic due to increased anaerobic respiration leading to irreversible cellular damage. Chemical exchange saturation transfer (CEST) effects can be used to generate pH-weighted magnetic resonance imaging (MRI) contrast, which has been used to delineate the ischemic penumbra after ischemic stroke. In the current study, a novel MRI ratiometric technique is presented to measure absolute pH using the ratio of CEST-mediated contrast from amine and amide protons: amine/amide concentration-independent detection (AACID). Effects of CEST were observed at 2.75 parts per million (p.p.m.) for amine protons and at 3.50 p.p.m. for amide protons downfield (i.e., higher frequency) from bulk water. Using numerical simulations and in vitro MRI experiments, we showed that pH measured using AACID was independent of tissue relaxation time constants, macromolecular magnetization transfer effects, protein concentration, and temperature within the physiologic range. After in vivo pH calibration using phosphorus (31P) magnetic resonance spectroscopy (31P-MRS), local acidosis is detected in mouse brain after focal permanent middle cerebral artery occlusion. In summary, our results suggest that AACID represents a noninvasive method to directly measure the spatial distribution of absolute pH in vivo using CEST MRI.
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Seyman, Estelle, David Kim, Aditya Bharatha, Courtney Casserly, Kristen Krysko, Roy-Hewitson Chantal, Paula Alcaide-Leon, Suradech Suthiphosuwan, and Jiwon Oh. "Quantitative spinal cord MRI and sexual dysfunction in multiple sclerosis." Multiple Sclerosis Journal - Experimental, Translational and Clinical 8, no. 4 (October 2022): 205521732211321. http://dx.doi.org/10.1177/20552173221132170.

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Background Sexual dysfunction (SD) is frequently reported in multiple sclerosis (MS) and is likely related to MS-related damage to the spinal cord (SC). Objective To assess associations between SD and quantitative MRI measures in people with MS (pwMS). Methods This pilot study included 17 pwMS with SD who completed questionnaires assessing SD, mood, and fatigue. All participants underwent brain, cervical, and thoracic SC-MRI at 3T. Quantitative brain and SC-MRI measures, including brain/SC atrophy, SC lesion count, diffusion-tensor imaging (DTI) indices (fractional anisotropy [FA], mean, perpendicular, parallel diffusivity [MD, λ⊥, λ||]) and magnetization-transfer ratio (MTR) were obtained. Associations between quantitative MRI measures and SD were assessed while controlling for the extent of mood and fatigue symptomatology. Results Subjects were a mean age of 46.9 years and 29% female. All subjects had self-reported SD (MSISQ-19 = 40.7, SQoL: 55.9) and 65% had a concurrent psychiatric diagnosis. When correlations between SD severity were assessed with individual brain and SC-MRI measures while controlling for psychiatric symptomatology, no associations were found. The only variables showing independent associations with SD were anxiety ( p = 0.03), depression ( p = 0.05), and fatigue ( p = 0.04). Conclusion We found no correlations between quantitative MRI measures in the brain and SC and severity of SD in pwMS, but psychiatric symptomatology and fatigue severity demonstrated relationships with SD. The multifactorial nature of SD in pwMS mandates a multidisciplinary approach.
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Bourbon-Teles, José, Sonya Bells, Derek K. Jones, Elizabeth Coulthard, Anne Rosser, and Claudia Metzler-Baddeley. "Myelin Breakdown in Human Huntington’s Disease: Multi-Modal Evidence from Diffusion MRI and Quantitative Magnetization Transfer." Neuroscience 403 (April 2019): 79–92. http://dx.doi.org/10.1016/j.neuroscience.2017.05.042.

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Fazekas, F., S. Ropele, C. Enzinger, T. Seifert, and S. Strasser-Fuchs. "Quantitative magnetization transfer imaging of pre-lesional white-matter changes in multiple sclerosis." Multiple Sclerosis Journal 8, no. 6 (December 2002): 479–84. http://dx.doi.org/10.1191/1352458502ms860oa.

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Objective: Previous magnetization transfer (MT) studies in multiple sclerosis (MS) suggest a reduction of the MT ratio (MTR) precedes new lesion development. To gain further insight into pre-lesional tissue abnormalities, we investigated the time course of additional quantitative MT parameters. Methods: Serial magnetic resonance imaging (MRI), including a gadolinium-enhanced T1 scan and MT imaging by means of a FastPACE sequence, was performed on 12 patients (4 males, 8 females) with relapsing-remitting MS. Quantitative MT values including the magnetization exchange rate (kfor) and the native relaxation time (T1free) were analysed in the six months prior to the appearance of 44 enhancing lesions and in 88 control regions of persistently normal-appearing white matter (NAWM). Results: Appearance of new active lesions was preceded by a significant decrease of the MTR (F7,166=91.5; p <0.0001) and of kfor (F7,166=105.2; p <0.0001), and by an increase of T1free (F7,166=57.3; p <0.0001). The drop of kfor was the most pronounced pre-lesional change and together with the MTR was statistically significant already four months before the appearance of new lesion. The observed increase of T1free was relatively small. MT variables of reactivated lesions were always different from NAWM but showed no characteristic time course. Conclusions: Multiparametric MT measurements suggest both a reduction of macromolecular material and a focal increase of free water to occur several months before the appearance of an active lesion. Reduction of the magnetization exchange rate, which may result from primary damage to myelin, appears to be the leading event.
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Bagnato, Francesca, Simon Hametner, Giulia Franco, Siddharama Pawate, Subramaniam Sriram, Hans Lassmann, John Gore, Seth E. Smith, and Richard Dortch. "Selective Inversion Recovery Quantitative Magnetization Transfer Brain MRI at 7T: Clinical and Postmortem Validation in Multiple Sclerosis." Journal of Neuroimaging 28, no. 4 (April 19, 2018): 380–88. http://dx.doi.org/10.1111/jon.12511.

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Valošek, Jan, Petr Bednařík, Miloš Keřkovský, Petr Hluštík, Josef Bednařík, and Alena Svátková. "Quantitative MR Markers in Non-Myelopathic Spinal Cord Compression: A Narrative Review." Journal of Clinical Medicine 11, no. 9 (April 20, 2022): 2301. http://dx.doi.org/10.3390/jcm11092301.

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Degenerative spinal cord compression is a frequent pathological condition with increasing prevalence throughout aging. Initial non-myelopathic cervical spinal cord compression (NMDC) might progress over time into potentially irreversible degenerative cervical myelopathy (DCM). While quantitative MRI (qMRI) techniques demonstrated the ability to depict intrinsic tissue properties, longitudinal in-vivo biomarkers to identify NMDC patients who will eventually develop DCM are still missing. Thus, we aim to review the ability of qMRI techniques (such as diffusion MRI, diffusion tensor imaging (DTI), magnetization transfer (MT) imaging, and magnetic resonance spectroscopy (1H-MRS)) to serve as prognostic markers in NMDC. While DTI in NMDC patients consistently detected lower fractional anisotropy and higher mean diffusivity at compressed levels, caused by demyelination and axonal injury, MT and 1H-MRS, along with advanced and tract-specific diffusion MRI, recently revealed microstructural alterations, also rostrally pointing to Wallerian degeneration. Recent studies also disclosed a significant relationship between microstructural damage and functional deficits, as assessed by qMRI and electrophysiology, respectively. Thus, tract-specific qMRI, in combination with electrophysiology, critically extends our understanding of the underlying pathophysiology of degenerative spinal cord compression and may provide predictive markers of DCM development for accurate patient management. However, the prognostic value must be validated in longitudinal studies.
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Trip, SA, PG Schlottmann, SJ Jones, W.-Y. Li, DF Garway-Heath, AJ Thompson, GT Plant, and DH Miller. "Optic nerve magnetization transfer imaging and measures of axonal loss and demyelination in optic neuritis." Multiple Sclerosis Journal 13, no. 7 (April 27, 2007): 875–79. http://dx.doi.org/10.1177/1352458507076952.

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Magnetization transfer imaging is an MRI technique that provides quantitative information about in vivo tissue integrity, including myelin and axonal content, and is expressed as the magnetization transfer ratio (MTR). The optic neuritis lesion can model the MS lesion in vivo and permits use of non-invasive markers of optic nerve myelination (visual evoked potential [VEP] latency) and retinal neuroaxonal loss (optical coherence tomography [OCT]) to provide further information about the in vivo substrates of optic nerve MTR. Twenty-five patients with optic neuritis were studied using an optic nerve MTR sequence, quantitative visual function testing, VEPs and OCT, along with 15 controls. MTR was reduced in affected nerves compared to both clinically unaffected nerves from patients and control nerves ( P < 0.001). Whole-nerve MTR correlated modestly with central-field VEP latency but more strongly when lesion-only MTR was measured, when a modest correlation with whole-field VEP latency emerged. OCT-quantified retinal neuroaxonal loss also correlated with MTR. In conclusion, markers of optic nerve myelination and axonal loss both correlate with optic nerve MTR. Because axonal loss following optic neuritis also results in myelin loss, the relative contributions of the two pathological conditions to the MTR measures cannot be estimated from this study. Multiple Sclerosis 2007; 13: 875—879. http://msj.sagepub.com
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Virostko, John, Richard C. Craddock, Jonathan M. Williams, Taylor M. Triolo, Melissa A. Hilmes, Hakmook Kang, Liping Du, et al. "Development of a standardized MRI protocol for pancreas assessment in humans." PLOS ONE 16, no. 8 (August 24, 2021): e0256029. http://dx.doi.org/10.1371/journal.pone.0256029.

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Magnetic resonance imaging (MRI) has detected changes in pancreas volume and other characteristics in type 1 and type 2 diabetes. However, differences in MRI technology and approaches across locations currently limit the incorporation of pancreas imaging into multisite trials. The purpose of this study was to develop a standardized MRI protocol for pancreas imaging and to define the reproducibility of these measurements. Calibrated phantoms with known MRI properties were imaged at five sites with differing MRI hardware and software to develop a harmonized MRI imaging protocol. Subsequently, five healthy volunteers underwent MRI at four sites using the harmonized protocol to assess pancreas size, shape, apparent diffusion coefficient (ADC), longitudinal relaxation time (T1), magnetization transfer ratio (MTR), and pancreas and hepatic fat fraction. Following harmonization, pancreas size, surface area to volume ratio, diffusion, and longitudinal relaxation time were reproducible, with coefficients of variation less than 10%. In contrast, non-standardized image processing led to greater variation in MRI measurements. By using a standardized MRI image acquisition and processing protocol, quantitative MRI of the pancreas performed at multiple locations can be incorporated into clinical trials comparing pancreas imaging measures and metabolic state in individuals with type 1 or type 2 diabetes.
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Giorgio, Antonio, Emilio Portaccio, Maria Laura Stromillo, Silvia Marino, Valentina Zipoli, Marco Battaglini, Anita Blandino, et al. "Cortical functional reorganization and its relationship with brain structural damage in patients with benign multiple sclerosis." Multiple Sclerosis Journal 16, no. 11 (July 29, 2010): 1326–34. http://dx.doi.org/10.1177/1352458510377333.

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Background: Patients with multiple sclerosis (MS) who have a favourable clinical status several years after disease onset are classified as ‘benign’. In many cases brain tissue damage does not differ between benign MS and the ‘classical’ MS forms. Objective: To assess whether the favourable clinical course in benign MS could be explained by the presence of an efficient functional cortical reorganization. Method: Twenty-five right-handed patients with benign MS (defined as having Expanded Disability Status Scale ≤ 3 and disease duration >15 years) underwent functional MRI during a simple motor task (right-hand tapping) to assess movement-associated brain activation. This was compared with that of 10 patients with relapsing—remitting MS and 10 normal controls. Benign MS patients also underwent conventional brain MRI and magnetization transfer imaging, which was compared with an identical examination obtained 1 year before. Quantitative structural magnetic resonance measures were baseline and changes over time in T2-lesion volume, magnetization transfer ratio in T2 lesions and normal-appearing brain and total brain volume. Results: Movement-related activation was greater in patients with benign MS than in those with relapsing—remitting MS or normal controls, extensively involving bilateral regions of the sensorimotor network as well as basal ganglia, insula and cerebellum. Greater activation correlated with lower T2-lesion magnetization transfer ratio, and with decreasing brain volume and increasing T2 lesion volume. Conclusions: The results suggest that bilateral brain networks, beyond those normally engaged in motor tasks, are recruited during a simple hand movement in patients with benign MS. This increased activation is probably the expression of an extensive, compensatory and tissue-damage related functional cortical reorganization. This can explain, at least in part, the favourable clinical expression of patients with benign MS.
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Koike, Hirofumi, Minoru Morikawa, Hideki Ishimaru, Reiko Ideguchi, Masataka Uetani, Takeshi Hiu, Takayuki Matsuo, and Mitsuharu Miyoshi. "Quantitative Chemical Exchange Saturation Transfer Imaging of Amide Proton Transfer Differentiates between Cerebellopontine Angle Schwannoma and Meningioma: Preliminary Results." International Journal of Molecular Sciences 23, no. 17 (September 5, 2022): 10187. http://dx.doi.org/10.3390/ijms231710187.

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Vestibular schwannomas are the most common tumor at the common cerebellopontine angle, followed by meningiomas. Differentiation of these tumors is critical because of the different surgical approaches required for treatment. Recent studies have demonstrated the utility of amide proton transfer (APT)-chemical exchange saturation transfer (CEST) imaging in evaluating malignant brain tumors. However, APT imaging has not been applied in benign tumors. Here, we explored the potential of APT in differentiating between schwannomas and meningiomas at the cerebellopontine angle. We retrospectively evaluated nine patients with schwannoma and nine patients with meningioma who underwent APT-CEST MRI from November 2020 to April 2022 pre-operation. All 18 tumors were histologically diagnosed. There was a significant difference in magnetization transfer ratio asymmetry (MTRasym) values (0.033 ± 0.012 vs. 0.021 ± 0.004; p = 0.007) between the schwannoma and meningioma groups. Receiver operative curve analysis showed that MTRasym values clearly differentiated between the schwannoma and meningioma groups. At an MTRasym value threshold of 0.024, the diagnostic sensitivity, specificity, positive predictive value, and negative predictive values for MTRasym were 88.9%, 77.8%, 80.0%, and 87.5%, respectively. Our results demonstrated the ability of MTRasym values on APT-CEST imaging to discriminate patients with schwannomas from patients with meningiomas.
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Vohra, Ravneet, Yak-Nam Wang, Helena Son, Stephanie Totten, Akshit Arora, Adam Maxwell, and Donghoon Lee. "Non-Invasive Monitoring of Increased Fibrotic Tissue and Hyaluronan Deposition in the Tumor Microenvironment in the Advanced Stages of Pancreatic Ductal Adenocarcinoma." Cancers 14, no. 4 (February 16, 2022): 999. http://dx.doi.org/10.3390/cancers14040999.

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Pancreatic ductal adenocarcinomas are characterized by a complex and robust tumor microenvironment (TME) consisting of fibrotic tissue, excessive levels of hyaluronan (HA), and immune cells. We utilized quantitative multi-parametric magnetic resonance imaging (mp-MRI) methods at 14 Tesla in a genetically engineered KPC (KrasLSL-G12D/+, Trp53LSL-R172H/+, Cre) mouse model to assess the complex TME in advanced stages of tumor development. The whole tumor, excluding cystic areas, was selected as the region of interest for data analysis and subsequent statistical analysis. Pearson correlation was used for statistical inference. There was a significant correlation between tumor volume and T2 (r = −0.66), magnetization transfer ratio (MTR) (r = 0.60), apparent diffusion coefficient (ADC) (r = 0.48), and Glycosaminoglycan-chemical exchange saturation transfer (GagCEST) (r = 0.51). A subset of mice was randomly selected for histological analysis. There were positive correlations between tumor volume and fibrosis (0.92), and HA (r = 0.76); GagCEST and HA (r = 0.81); and MTR and CD31 (r = 0.48). We found a negative correlation between ADC low-b (perfusion) and Ki67 (r = −0.82). Strong correlations between mp-MRI and histology results suggest that mp-MRI can be used as a non-invasive tool to monitor the tumor microenvironment.
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Ozturk, A., SA Smith, EM Gordon-Lipkin, DM Harrison, N. Shiee, DL Pham, BS Caffo, PA Calabresi, and DS Reich. "MRI of the corpus callosum in multiple sclerosis: association with disability." Multiple Sclerosis Journal 16, no. 2 (February 2010): 166–77. http://dx.doi.org/10.1177/1352458509353649.

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Inflammatory demyelination and axon damage in the corpus callosum are prominent features of multiple sclerosis (MS) and may partially account for impaired performance on complex tasks. The objective of this article was to characterize quantitative callosal MRI abnormalities and their association with disability. In 69 participants with MS and 29 healthy volunteers, lesional and extralesional callosal MRI indices were estimated via diffusion tensor tractography. expanded disability status scale (EDSS) and MS functional composite (MSFC) scores were recorded in 53 of the participants with MS. All tested callosal MRI indices were diffusely abnormal in MS. EDSS score was correlated only with age (r = 0.51). Scores on the overall MSFC and its paced serial auditory addition test (PASAT) and 9-hole peg test components were correlated with callosal fractional anisotropy (r = 0.27, 0.35, and 0.31, respectively) and perpendicular diffusivity (r = —0.29, —0.30, and —0.31) but not with overall callosal volume or callosal lesion volume; the PASAT score was more weakly correlated with callosal magnetization-transfer ratio (r = 0.21). Anterior callosal abnormalities were associated with impaired PASAT performance and posterior abnormalities with slow performance on the 9-hole peg test. In conclusion, abnormalities in the corpus callosum can be assessed with quantitative MRI and are associated with cognitive and complex upper-extremity dysfunction in MS.
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Reuter, Gilles, Emilie Lommers, Evelyne Balteau, Jessica Simon, Christophe Phillips, Felix Scholtes, Didier Martin, Arnaud Lombard, and Pierre Maquet. "Multiparameter quantitative histological MRI values in high-grade gliomas: a potential biomarker of tumor progression." Neuro-Oncology Practice 7, no. 6 (August 15, 2020): 646–55. http://dx.doi.org/10.1093/nop/npaa047.

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Abstract Background Conventional MRI poorly distinguishes brain parenchyma microscopically invaded by high-grade gliomas (HGGs) from the normal brain. By contrast, quantitative histological MRI (hMRI) measures brain microstructure in terms of physical MR parameters influenced by histochemical tissue composition. We aimed to determine the relationship between hMRI parameters in the area surrounding the surgical cavity and the presence of HGG recurrence. Methods Patients were scanned after surgery with an hMRI multiparameter protocol that allowed for estimations of longitudinal relaxation rate (R1) = 1/T1, effective transverse relaxation rate (R2)*=1/T2*, magnetization transfer saturation (MTsat), and proton density. The initial perioperative zone (IPZ) was segmented on the postoperative MRI. Once recurrence appeared on conventional MRI, the area of relapsing disease was delineated (extension zone, EZ). Conventional MRI showing recurrence and hMRI were coregistered, allowing for the extraction of parameters R1, R2*, MTsat, and PD in 3 areas: the overlap area between the IPZ and EZ (OZ), the peritumoral brain zone, PBZ (PBZ = IPZ – OZ), and the area of recurrence (RZ = EZ – OZ). Results Thirty-one patients with HGG who underwent gross-total resection were enrolled. MTsat and R1 were the most strongly associated with tumor progression. MTsat was significantly lower in the OZ and RZ, compared to PBZ. R1 was significantly lower in RZ compared to PBZ. PD was significantly higher in OZ compared to PBZ, and R2* was higher in OZ compared to PBZ or RZ. These changes were detected 4 to 120 weeks before recurrence recognition on conventional MRI. Conclusions HGG recurrence was associated with hMRI parameters’ variation after initial surgery, weeks to months before overt recurrence.
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Mascalchi, Mario, Stefano Ciulli, Andrea Bianchi, Chiara Marzi, Stefano Orsolini, Gioele Gavazzi, Marco Aiello, et al. "Handedness Side and Magnetization Transfer Ratio in the Primary Sensorimotor Cortex Central Sulcus." BioMed Research International 2019 (August 5, 2019): 1–7. http://dx.doi.org/10.1155/2019/5610849.

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Left-handers show lower asymmetry in manual ability when compared to right-handers. Unlike right-handers, left-handers do not show larger deactivation of the ipsilateral primary sensorimotor (SM1) cortex on functional magnetic resonance imaging when moving their dominant than their nondominant hand. However, it should be noted that morphometric MRI studies have reported no differences between right-handers and left-handers in volume, thickness, or surface area of the SM1 cortex. In this regard, magnetization transfer (MT) imaging is a technique with the potential to provide information on microstructural organization and macromolecular content of tissue. In particular, MT ratio index of the brain gray matter is assumed to reflect the variable content of afferent or efferent myelinated fibers, with higher MT ratio values being associated with increased fibers number or degree of myelination. The aim of this study was hence to assess, for the first time, through quantitative MT ratio measurements, potential differences in microstructural organization/characteristics of SM1 cortex between left- and right-handers, which could underlay handedness side. Nine left-handed and 9 right-handed healthy subjects, as determined by the Edinburgh handedness inventory, were examined with T1-weighted and MT-weighted imaging on a 3 T scanner. The hands of subjects were kept still during all acquisitions. Using FreeSurfer suite and the automatic anatomical labeling parcellations defined by the Destrieux atlas, we measured MT ratio, as well as cortical thickness, in three regions of interests corresponding to the precentral gyrus, the central sulcus, and the postcentral gyrus in the bilateral SM1 cortex. No significant difference between left- and right-handers was revealed in the thickness of the three partitions of the SM1 cortex. However, left-handers showed a significantly (p = 0.007) lower MT ratio (31.92% ± 0.96%) in the right SM1 central sulcus (i.e., the hand representation area for left-handers) as compared to right-handers (33.28% ± 0.94%). The results of this preliminary study indicate that quantitative MT imaging, unlike conventional morphometric MRI measurements, can be a useful tool to reveal, in SM1 cortex, potential microstructural correlates of handedness side.
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Ross, Brian D., Dariya Malyarenko, Kevin Heist, Ghoncheh Amouzandeh, Youngsoon Jang, Christopher A. Bonham, Cyrus Amirfazli, Gary D. Luker, and Thomas L. Chenevert. "Repeatability of Quantitative Magnetic Resonance Imaging Biomarkers in the Tibia Bone Marrow of a Murine Myelofibrosis Model." Tomography 9, no. 2 (February 28, 2023): 552–66. http://dx.doi.org/10.3390/tomography9020045.

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Quantitative MRI biomarkers are sought to replace painful and invasive sequential bone-marrow biopsies routinely used for myelofibrosis (MF) cancer monitoring and treatment assessment. Repeatability of MRI-based quantitative imaging biomarker (QIB) measurements was investigated for apparent diffusion coefficient (ADC), proton density fat fraction (PDFF), and magnetization transfer ratio (MTR) in a JAK2 V617F hematopoietic transplant model of MF. Repeatability coefficients (RCs) were determined for three defined tibia bone-marrow sections (2–9 mm; 10–12 mm; and 12.5–13.5 mm from the knee joint) across 15 diseased mice from 20–37 test-retest pairs. Scans were performed on consecutive days every two weeks for a period of 10 weeks starting 3–4 weeks after transplant. The mean RC with (95% confidence interval (CI)) for these sections, respectively, were for ADC: 0.037 (0.031, 0.050), 0.087 (0.069, 0.116), and 0.030 (0.022, 0.044) μm2/ms; for PDFF: 1.6 (1.3, 2.0), 15.5 (12.5, 20.2), and 25.5 (12.0, 33.0)%; and for MTR: 0.16 (0.14, 0.19), 0.11 (0.09, 0.15), and 0.09 (0.08, 0.15). Change-trend analysis of these QIBs identified a dynamic section within the mid-tibial bone marrow in which confident changes (exceeding RC) could be observed after a four-week interval between scans across all measured MRI-based QIBs. Our results demonstrate the capability to derive quantitative imaging metrics from mouse tibia bone marrow for monitoring significant longitudinal MF changes.
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Jonkman, Laura E., Lazar Fleysher, Martijn D. Steenwijk, Jan A. Koeleman, Teun-Pieter de Snoo, Frederik Barkhof, Matilde Inglese, and Jeroen JG Geurts. "Ultra-high field MTR and qR2* differentiates subpial cortical lesions from normal-appearing gray matter in multiple sclerosis." Multiple Sclerosis Journal 22, no. 10 (July 20, 2016): 1306–14. http://dx.doi.org/10.1177/1352458515620499.

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Background: Cortical gray matter (GM) demyelination is frequent and clinically relevant in multiple sclerosis (MS). Quantitative magnetic resonance imaging (qMRI) sequences such as magnetization transfer ratio (MTR) and quantitative R2* (qR2*) can capture pathological subtleties missed by conventional magnetic resonance imaging (MRI) sequences. Although differences in MTR and qR2* have been reported between lesional and non-lesional tissue, differences between lesion types or lesion types and myelin density matched normal-appearing gray matter (NAGM) have not been found or investigated. Objective: Identify quantitative differences in histopathologically verified GM lesion types and matched NAGM at ultra-high field strength. Methods: Using 7T post-mortem MRI, MRI lesions were marked on T2 images and co-registered to the calculated MTR and qR2* maps for further evaluation. In all, 15 brain slices were collected, containing a total of 74 cortical GM lesions and 45 areas of NAGM. Results: Intracortical lesions had lower MTR and qR2* values compared to NAGM. Type I lesions showed lower MTR than type III lesions. Type III lesions showed lower MTR than matched NAGM, and type I and IV lesions showed lower qR2* than matched NAGM. Conclusion: qMRI at 7T can provide additional information on extent of cortical pathology, especially concerning subpial lesions. This may be relevant for monitoring disease progression and potential treatment effects.
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Rausch, M., PS Tofts, P. Lervik, AR Walmsley, A. Mir, A. Schubart, and T. Seabrook. "Characterization of white matter damage in animal models of multiple sclerosis by magnetization transfer ratio and quantitative mapping of the apparent bound proton fraction f*." Multiple Sclerosis Journal 15, no. 1 (January 2009): 16–27. http://dx.doi.org/10.1177/1352458508096006.

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Quantitative magnetization transfer magnetic resonance imaging (qMT-MRI) can be used to improve detection of white matter tissue damage in multiple sclerosis (MS) and animal models thereof. To study the correlation between MT parameters and tissue damage, the magnetization transfer ratio (MTR), the parameter f* (closely related to the bound proton fraction) and the bound proton transverse relaxation time T2B of lesions in a model of focal experimental autoimmune encephalomyelitis (EAE) were measured on a 7T animal scanner and data were compared with histological markers indicative for demyelination, axonal density, and tissue damage. A clear spatial correspondence was observed between reduced values of MTR and demyelination in this animal model. We observed two different levels of MTR and f* reduction for these lesions. One was characterized by a pronounced demyelination and the other corresponded to a more severe loss of the cellular matrix. Changes in f* were generally more pronounced than those of MTR in areas of demyelination. Moreover, a reduction of f* was already observed for tissue where MTR was virtually normal. No changes in T2B were observed for the lesions. We conclude that MTR and qMT mapping are efficient and reliable readouts for studying demyelination in animal models of MS, and that the analysis of regional f* might be even superior to the analysis of MTR values. Therefore, quantitative mapping of f* from human brains might also improve the detection of white matter damage in MS.
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Alsop, D. C., and J. A. Detre. "Reduced Transit-Time Sensitivity in Noninvasive Magnetic Resonance Imaging of Human Cerebral Blood Flow." Journal of Cerebral Blood Flow & Metabolism 16, no. 6 (November 1996): 1236–49. http://dx.doi.org/10.1097/00004647-199611000-00019.

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Herein, we present a theoretical framework and experimental methods to more accurately account for transit effects in quantitative human perfusion imaging using endogenous magnetic resonance imaging (MRI) contrast. The theoretical transit time sensitivities of both continuous and pulsed inversion spin tagging experiments are demonstrated. We propose introducing a delay following continuous labeling, and demonstrate theoretically that introduction of a delay dramatically reduces the transit time sensitivity of perfusion imaging. The effects of magnetization transfer saturation on this modified continuous labeling experiment are also derived, and the assumption that the perfusion signal resides entirely within tissue rather than the arterial microvasculature is examined. We present results demonstrating the implementation of the continuous tagging experiment with delay on an echoplanar scanner for measuring cerebral blood flow (CBF) in normal volunteers. By varying the delay, we estimate transit times in the arterial system, values that are necessary for assessing the accuracy of our quantification. The effect of uncertainties in the transit time from the tagging plane to the arterial microvasculature and the transit time to the tissue itself on the accuracy of perfusion quantification is discussed and found to be small in gray matter but still potentially significant in white matter. A novel method for measuring T1, which is fast, insensitive to contamination by cerebrospinal fluid, and compatible with the application of magnetization transfer saturation, is also presented. The methods are combined to produce quantitative maps of resting and hypercarbic CBF.
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Casella, Chiara, Jose Bourbon-Teles, Sonya Bells, Elizabeth Coulthard, Greg D. Parker, Anne Rosser, Derek K. Jones, and Claudia Metzler-Baddeley. "Drumming Motor Sequence Training Induces Apparent Myelin Remodelling in Huntington’s Disease: A Longitudinal Diffusion MRI and Quantitative Magnetization Transfer Study." Journal of Huntington's Disease 9, no. 3 (October 8, 2020): 303–20. http://dx.doi.org/10.3233/jhd-200424.

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Background: Impaired myelination may contribute to Huntington’s disease (HD) pathogenesis. Objective: This study assessed differences in white matter (WM) microstructure between HD patients and controls, and tested whether drumming training stimulates WM remodelling in HD. Furthermore, it examined whether training-induced microstructural changes are related to improvements in motor and cognitive function. Methods: Participants undertook two months of drumming exercises. Working memory and executive function were assessed before and post-training. Changes in WM microstructure were investigated with diffusion tensor magnetic resonance imaging (DT-MRI)-based metrics, the restricted diffusion signal fraction (Fr) from the composite hindered and restricted model of diffusion (CHARMED) and the macromolecular proton fraction (MPF) from quantitative magnetization transfer (qMT) imaging. WM pathways linking putamen and supplementary motor areas (SMA-Putamen), and three segments of the corpus callosum (CCI, CCII, CCIII) were studied using deterministic tractography. Baseline MPF differences between patients and controls were assessed with tract-based spatial statistics. Results: MPF was reduced in the mid-section of the CC in HD subjects at baseline, while a significantly greater change in MPF was detected in HD patients relative to controls in the CCII, CCIII, and the right SMA-putamen post-training. Further, although patients improved their drumming and executive function performance, such improvements did not correlate with microstructural changes. Increased MPF suggests training-induced myelin changes in HD. Conclusion: Though only preliminary and based on a small sample size, these results suggest that tailored behavioural stimulation may lead to neural benefits in early HD, that could be exploited for delaying disease progression.
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Cloney, Michael Brendan, Zachary A. Smith, Kenneth A. Weber, and Todd B. Parrish. "Quantitative Magnetization Transfer MRI Measurements of the Anterior Spinal Cord Region are Associated With Clinical Outcomes in Cervical Spondylotic Myelopathy." SPINE 43, no. 10 (May 2018): 675–80. http://dx.doi.org/10.1097/brs.0000000000002470.

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Nossin-Manor, Revital, Dallas Card, Drew Morris, Salma Noormohamed, Manohar M. Shroff, Hilary E. Whyte, Margot J. Taylor, and John G. Sled. "Quantitative MRI in the very preterm brain: Assessing tissue organization and myelination using magnetization transfer, diffusion tensor and T1 imaging." NeuroImage 64 (January 2013): 505–16. http://dx.doi.org/10.1016/j.neuroimage.2012.08.086.

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Piper, Rory J., Shadia Mikhael, Joanna M. Wardlaw, David H. Laidlaw, Ian R. Whittle, and Mark E. Bastin. "Imaging signatures of meningioma and low-grade glioma: a diffusion tensor, magnetization transfer and quantitative longitudinal relaxation time MRI study." Magnetic Resonance Imaging 34, no. 4 (May 2016): 596–602. http://dx.doi.org/10.1016/j.mri.2015.12.006.

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43

van de Stadt, Stephanie I. W., Irene C. Huffnagel, Bela R. Turk, Marjo S. van der Knaap, and Marc Engelen. "Imaging in X-Linked Adrenoleukodystrophy." Neuropediatrics 52, no. 04 (June 30, 2021): 252–60. http://dx.doi.org/10.1055/s-0041-1730937.

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AbstractMagnetic resonance imaging (MRI) is the gold standard for the detection of cerebral lesions in X-linked adrenoleukodystrophy (ALD). ALD is one of the most common peroxisomal disorders and is characterized by a defect in degradation of very long chain fatty acids (VLCFA), resulting in accumulation of VLCFA in plasma and tissues. The clinical spectrum of ALD is wide and includes adrenocortical insufficiency, a slowly progressive myelopathy in adulthood, and cerebral demyelination in a subset of male patients. Cerebral demyelination (cerebral ALD) can be treated with hematopoietic cell transplantation (HCT) but only in an early (pre- or early symptomatic) stage and therefore active MRI surveillance is recommended for male patients, both pediatric and adult. Although structural MRI of the brain can detect the presence and extent of cerebral lesions, it does not predict if and when cerebral demyelination will occur. There is a great need for imaging techniques that predict onset of cerebral ALD before lesions appear. Also, imaging markers for severity of myelopathy as surrogate outcome measure in clinical trials would facilitate drug development. New quantitative MRI techniques are promising in that respect. This review focuses on structural and quantitative imaging techniques—including magnetic resonance spectroscopy, diffusion tensor imaging, MR perfusion imaging, magnetization transfer (MT) imaging, neurite orientation dispersion and density imaging (NODDI), and myelin water fraction imaging—used in ALD and their role in clinical practice and research opportunities for the future.
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Syc, Stephanie B., Daniel M. Harrison, Shiv Saidha, Michaela Seigo, Peter A. Calabresi, and Daniel S. Reich. "Quantitative MRI Demonstrates Abnormality of the Fornix and Cingulum in Multiple Sclerosis." Multiple Sclerosis International 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/838719.

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Objective. To characterize MR signal changes associated with tissue damage in the fornix and cingulum in multiple sclerosis (MS) using quantitative MRI measures and to determine associations with cognitive dysfunction.Background. The fornix and cingulum are white-matter bundles that carry information related to cognition. While cognitive dysfunction is reported in 40–60% of MS patients, the neuroanatomical correlates of cognitive impairment remain incompletely understood.Methods. The cingulum, pillars of the fornix, and corticospinal tract were segmented by fiber tracking via diffusion tensor imaging. Average tract-specific fractional anisotropy (FA), mean diffusivity (MD), and magnetization transfer ratio (MTR) were compared in MS cases and healthy volunteers. Associations with clinical measures and neuropsychological tests were derived by multivariate linear regression.Results. Fornix FA (P=0.004) and MTR (P=0.005) were decreased, and fornix MD (P<0.001) and cingulum MD (P<0.001) increased, in MS cases (n=101) relative to healthy volunteers (n=16) after adjustment for age and sex. Lower fornix FA and MTR, and higher fornix MD andλ∥, were correlated with lower PASAT-3 scores, but not with slower 25FTW times. Lower PASAT-3 scores were associated with lower cingulum FA and higher MD andλ⊥.Conclusions. Cognitive dysfunction in MS may involve damage to a widespread network of brain structures, including white-matter pathways within the limbic system.
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Athertya, Jiyo S., Yajun Ma, Amir Masoud Afsahi, Alecio F. Lombardi, Dina Moazamian, Saeed Jerban, Sam Sedaghat, and Hyungseok Jang. "Accelerated Quantitative 3D UTE-Cones Imaging Using Compressed Sensing." Sensors 22, no. 19 (October 1, 2022): 7459. http://dx.doi.org/10.3390/s22197459.

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In this study, the feasibility of accelerated quantitative Ultrashort Echo Time Cones (qUTE-Cones) imaging with compressed sensing (CS) reconstruction is investigated. qUTE-Cones sequences for variable flip angle-based UTE T1 mapping, UTE adiabatic T1ρ mapping, and UTE quantitative magnetization transfer modeling of macromolecular fraction (MMF) were implemented on a clinical 3T MR system. Twenty healthy volunteers were recruited and underwent whole-knee MRI using qUTE-Cones sequences. The k-space data were retrospectively undersampled with different undersampling rates. The undersampled qUTE-Cones data were reconstructed using both zero-filling and CS reconstruction. Using CS-reconstructed UTE images, various parameters were estimated in 10 different regions of interests (ROIs) in tendons, ligaments, menisci, and cartilage. Structural similarity, percentage error, and Pearson’s correlation were calculated to assess the performance. Dramatically reduced streaking artifacts and improved SSIM were observed in UTE images from CS reconstruction. A mean SSIM of ~0.90 was achieved for all CS-reconstructed images. Percentage errors between fully sampled and undersampled CS-reconstructed images were below 5% for up to 50% undersampling (i.e., 2× acceleration). High linear correlation was observed (>0.95) for all qUTE parameters estimated in all subjects. CS-based reconstruction combined with efficient Cones trajectory is expected to achieve a clinically feasible scan time for qUTE imaging.
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Fox, Robert J., Elizabeth Fisher, Jean Tkach, Jar-Chi Lee, Jeffrey A. Cohen, and Richard A. Rudick. "Brain atrophy and magnetization transfer ratio following methylprednisolone in multiple sclerosis: short-term changes and long-term implications." Multiple Sclerosis Journal 11, no. 2 (April 2005): 140–45. http://dx.doi.org/10.1191/1352458505ms1142oa.

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Background: The short-term effect of corticosteroids on MRI measures of multiple sclerosis (MS) is not well understood and may have a significant impact when using these quantitative measures to evaluate disease activity and changes following other therapeutic interventions. Objective: To determine the impact of a course of intravenous methylprednisolone (IVMP) on quantitative measures of disease activity and tissue injury in MS patients. Methods: We prospectively measured brain parenchymal fraction (BPF), magnetization transfer ratio (MTR, lesional and whole brain), and lesion volumes on nine weekly brain MRI studies in ten MS patients receiving a course of IVMP. A group of nine MS patients not receiving IVMP served as controls. Results: In comparison to untreated controls, BPF declined over the eight weeks following IVMP treatment (P<0.02). BPF decline was most prominent in patients with secondary progressive MS (SPMS, P<0.03), and was not seen in relapsing-remitting (RR) MS patients. Short-term change in BPF correlated with baseline BPF (r=0.62, P=0.05) and short-term change in lesional MTR (r=-0.55, P=0.03), but not with change in enhancing lesion volume. Short-term change in lesional MTR inversely correlated with baseline lesional and whole brain MTR (r=-0.79, P=0.04 for both). There was no significant difference between treated and control patients in measures of MTR or T2, T1 or enhancing lesion volumes. Conclusions: Patients with SPMS showed a greater decline in BPF following IVMP than RRMS patients. A correlation between changes in BPF and MTR suggest that these changes are secondary to altered water content within MS lesions. Differential response to a standardized therapeutic intervention in RRMS and SPMS suggests that responses to therapy may differ due to a fundamental pathologic difference between early and late stage MS.
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Saccenti, Laetitia, Akifumi Hagiwara, Christina Andica, Kazumasa Yokoyama, Shohei Fujita, Shimpei Kato, Tomoko Maekawa, et al. "Myelin Measurement Using Quantitative Magnetic Resonance Imaging: A Correlation Study Comparing Various Imaging Techniques in Patients with Multiple Sclerosis." Cells 9, no. 2 (February 8, 2020): 393. http://dx.doi.org/10.3390/cells9020393.

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Evaluation of myelin by magnetic resonance imaging (MRI) is a difficult challenge, but holds promise in demyelinating diseases, such as multiple sclerosis (MS). Although multiple techniques have been developed, no gold standard has been established. This study aims to evaluate the correlation between synthetic MRI myelin volume fraction (SyMRIMVF) and myelin fraction estimated by other techniques, i.e., magnetization transfer saturation (MTsat), T1-weighted images divided by T2-weighted images (T1w/T2w), and radial diffusivity (RD) in patients with MS. We also compared the sensitivities of these techniques for detecting MS-related myelin damage. SyMRIMVF, MTsat, T1w/T2w, and RD were averaged on plaque, periplaque white matter, and normal-appearing white matter (NAWM). Pairwise correlation was calculated using Spearman’s correlation analysis. For all segmented regions, strong correlations were found between SyMRIMVF and T1w/T2w (Rho = 0.89), MTsat (Rho = 0.82), or RD (Rho = −0.75). For each technique, the average estimated myelin differed significantly among regions, but the percentage change of NAWM from both periplaque white matter and plaque were highest in SyMRIMVF. SyMRIMVF might be suitable for myelin evaluation in MS patients, with relevant results as compared to other well-studied techniques. Moreover, it presented better sensitivity for the detection of the difference between plaque or periplaque white matter and NAWM.
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Oh, Jiwon, Kathleen Zackowski, Min Chen, Scott Newsome, Shiv Saidha, Seth A. Smith, Marie Diener-West, et al. "Multiparametric MRI correlates of sensorimotor function in the spinal cord in multiple sclerosis." Multiple Sclerosis Journal 19, no. 4 (August 13, 2012): 427–35. http://dx.doi.org/10.1177/1352458512456614.

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Background: Spinal cord (SC) pathology is a major contributor to clinical disability in multiple sclerosis (MS). Conventional magnetic resonance imaging (MRI), specifically SC-MRI lesion load measures that include lesion count and volume, demonstrate only a modest relationship with the clinical status of MS patients. Although SC cross-sectional area (CSA) correlates better with clinical dysfunction than MRI lesion count, SC atrophy likely signifies irreversible tissue loss. Using quantitative MRI indices sensitive to early and late microstructural changes in the spinal cord, we searched for the presence of better correlations between MRI measures and clinical status in MS. Objectives: We investigated whether diffusion-tensor imaging indices and the magnetization-transfer ratio (MTR) were better associated with the clinical status of MS patients than conventional SC-MRI measures. Methods: A total of 129 MS patients underwent 3-tesla cervical SC-MRI and quantitative sensorimotor function testing, using the Vibratron-II and dynamometer. Regions-of-interest circumscribed the SC on axial slices between C3-C4. We calculated SC-CSA, fractional anisotropy (FA), mean diffusivity (MD), perpendicular diffusivity (λ⊥), parallel diffusivity (λ||) and MTR. We used multivariable linear regression to determine if there were any associations between MRI indices and clinical measures of dysfunction. Results: All MRI indices were significantly different in subjects with MS versus healthy controls, and between the progressive versus relapsing MS subtypes, with the exception of λ||. In multivariable regression models that were adjusted for age, sex, brain parenchymal fraction, and SC-CSA, the MRI indices independently explained variability in hip flexion strength ( p-values: MD, λ⊥, λ|| < 0.001; FA = 0.07), vibration sensation threshold ( p-values: FA = 0.04; MTR = 0.05; λ⊥ = 0.06), and Expanded Disability Status Scale scores ( p-values: FA = 0.003; MD = 0.03; λ⊥ = 0.005; MTR = 0.02). Conclusions: In a large, heterogeneous MS sample, quantitative SC-MRI indices demonstrated independent associations with system-specific and global clinical dysfunction. Our findings suggest that the indices studied may provide important information about microstructural SC changes and the substrates of limb disability in MS. The identified structure-function relationships underpin the potential utility of these measures in assessments of therapeutic efficacy.
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Cloney, Michael Brendan, Andy C. Smith, Kenneth Weber, Meijing Wu, Taylor Coffey, Alex Barry, Benjamin P. Liu, et al. "356 Quantitative Magnetization Transfer MRI Measurements of the Anterior Spinal Cord Region are Associated with Clinical Outcomes in Cervical Spondylotic Myelopathy." Neurosurgery 64, CN_suppl_1 (August 24, 2017): 281–82. http://dx.doi.org/10.1093/neuros/nyx417.356.

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Abstract INTRODUCTION Magnetization transfer ratio (MTR) is a quantitative measure that correlates with myelin loss and neural tissue destruction in a variety of neurological diseases. For example, in patients with multiple sclerosis, MTR of white matter lesions may predict clinical disability. However, the usefulness of MTR in patients with cervical spondylotic myelopathy (CSM) has not been examined. METHODS We prospectively enrolled seven CSM patients and seven age-matched controls to undergo MRI imaging of the cervical spine. Nurick, Neck Disability Index (NDI), and modified Japanese Orthopedic Association (mJOA) scores were collected for all patients. Clinical hyperreflexia was tested at the MCP joint, using a 6-axis load cell. Reflex was simulated by quickly moving the joint from maximum flexion to maximum extension (300 °/sec). Anterior, lateral, and posterior cord MTR measurements were compared to clinical outcomes. RESULTS >Compared to controls, CSM patients had lower anterior cord MTR (38.29 v. 29.97, ? = −8.314, P = 0.0022), and equivalent posterior cord (P = 0.2896) and lateral cord (P = 0.3062) MTR. Higher Nurick scores were associated with lower anterior cord MTR (P = 0.0205), but not lateral cord (P = 0.5446) or posterior cord MTR (P = 0.1222). Lower mJOA was associated with lower anterior cord MTR (P = 0.0090), but not lateral cord (P = 0.4864) or posterior cord MTR (P = 0.4819). There was no association between NDI and MTR of the anterior (P = 0.4351), lateral (P = 0.7557), or posterior cord (P = 0.9171). There was a linear relationship between hyperreflexia and anterior cord MTR (slope = −117.3, R = 0.6598, P = 0.0379), but not lateral cord (P = 0.1906, R = 0.4511) or posterior cord (P = 0.2577, R = 0.3957) MTR. CONCLUSION Anterior cord MTR correlates with clinical outcomes as measured by mJOA index, Nurick score, and quantitative hyperreflexia. Anterior cord MTR is associated with clinically relevant hyperreflexia, and could play a role in the preoperative assessment of CSM. Understanding this radiological metric may refine surgical decision-making.
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Charil, A., D. Caputo, R. Cavarretta, M. P. Sormani, P. Ferrante, and M. Filippi. "Cervical cord magnetization transfer ratio and clinical changes over 18 months in patients with relapsing-remitting multiple sclerosis: a preliminary study." Multiple Sclerosis Journal 12, no. 5 (September 2006): 662–65. http://dx.doi.org/10.1177/1352458506070714.

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Background Magnetization transfer ratio (MTR) permits the quantitative estimation of cervical cord tissue damage in patients with multiple sclerosis (MS). Objective To determine whether a single time-point MTR scan of the cervical cord is associated with short-term disease evolution in patients with relapsing-remitting (RR) MS. Methods Using a 1.5-T magnetic resonance imaging (MRI) system with a tailored cervical cord phased array coil, fast short-tau inversion recovery (fast-STIR) and MTR scans were obtained from 14 untreated patients with RRMS at baseline. Cervical cord MTR histograms were derived. Over the 18- month follow-up period, relapse rate was measured and disability assessed by the Expanded Disability Status Scale (EDSS) score. Results Average cervical cord MTR was correlated with relapse rate ( r= -0.56, P = 0.037). A moderate correlation ( r values ranging from -0.33 to -0.36) between baseline cervical cord MTR metrics and EDSS changes over 18 months was also noted, albeit statistical significance was not reached ( P = 0.26 and 0.21, respectively) perhaps because of the relatively small sample size. Conclusions This study suggests that a ‘snapshot’ MT MRI assessment of the cervical cord may detect cervical cord tissue changes associated with short-term disease evolution in RRMS.
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