Testing quantitative magnetization transfer models with membrane lipids.

PURPOSE: Quantitative magnetization transfer (qMT) models aim to quantify the contributions of lipids and macromolecules to the MRI signal. Hence, a model system that relates qMT parameters and their molecular sources may improve the interpretation of the qMT parameters. Here we used membrane lipid phantoms as a meaningful tool to study qMT models. By controlling the fraction and type of membrane lipids, we could test the accuracy, reliability, and interpretability of different qMT models. METHODS: We formulated liposomes with various lipid types and water-to-lipids fractions and measured their signals with spoiled gradient-echo MT. We fitted three known qMT models and estimated six parameters for every model. We tested the accuracy and reproducibility of the models and compared the dependency among the qMT parameters. We compared the samples' qMT parameters with their water-to-lipid fractions and with a simple MTnorm (= MTon/MToff) calculation. RESULTS: We found that the three qMT models fit the membrane lipids signals well. We also found that the estimated qMT parameters are highly interdependent. Interestingly, the estimated qMT parameters are a function of the membrane lipid type and also highly related to the water-to-lipid fraction. Finally, we find that most of the lipid sample's information can be captured using the common and easy to estimate MTnorm analysis. CONCLUSION: qMT parameters are sensitive to both the water-to-lipid fraction and to the lipid type. Estimating the water-to-lipid fraction can improve the characterization of membrane lipids' contributions to qMT parameters. Similar characterizations can be obtained using the MTnorm analysis.

Towards assessing and improving the reliability of ultrashort echo time quantitative magnetization transfer (UTE-qMT) MRI of cortical bone: In silico and ex vivo study.

OBJECTIVE: To assess and improve the reliability of the ultrashort echo time quantitative magnetization transfer (UTE-qMT) modeling of the cortical bone. MATERIALS AND METHODS: Simulation-based digital phantoms were created that mimic the UTE-qMT properties of cortical bones. A wide range of SNR from 25 to 200 was simulated by adding different levels of noise to the synthesized MT-weighted images to assess the effect of SNR on UTE-qMT fitting results. Tensor-based denoising algorithm was applied to improve the fitting results. These results from digital phantom studies were validated via ex vivo rat leg bone scans. RESULTS: The selection of initial points for nonlinear fitting and the number of data points tested for qMT analysis have minimal effect on the fitting result. Magnetization exchange rate measurements are highly dependent on the SNR of raw images, which can be substantially improved with an appropriate denoising algorithm that gives similar fitting results from the raw images with an 8-fold higher SNR. DISCUSSION: The digital phantom approach enables the assessment of the reliability of bone UTE-qMT fitting by providing the known ground truth. These findings can be utilized for optimizing the data acquisition and analysis pipeline for UTE-qMT imaging of cortical bones.

Noninvasively differentiating acute and chronic nephropathies via multiparametric urea-CEST, nuclear Overhauser enhancement-CEST, and quantitative magnetization transfer MRI.

PURPOSE: Standardized blood tests often lack adequate sensitivity and specificity to capture the gradual progression of renal injuries. We suggest a multiparametric molecular MRI approach as a noninvasive tool for monitoring renal function loss and distinguishing different types of renal injuries. METHODS: CEST and quantitative magnetization transfer (qMT) imaging were performed on cisplatin (n = 16) and aristolochic acid (AA)-induced nephropathy (n = 22) mouse models at 7T with an infusion of either saline or urea. Seven-pool Lorentzian fitting was applied for the analysis of CEST Z-spectra, and the T1 -corrected CEST contrast apparent exchange-dependent relaxation (AREX) from urea (+1 ppm) and two nuclear Overhauser enhancement (NOE) pools (-1.6 and -3.5 ppm) were measured. Similarly, qMT spectra were fitted into two-pool Ramani equation and the relative semi-solid macromolecular pool-size ratio was measured. Histology of mouse kidneys was performed to validate the MR findings. RESULTS: AA model showed disrupted spatial gradients of urea in the kidney and significantly decreased NOE CEST and qMT contrast. The cisplatin model showed slightly decreased qMT contrast only. The orrelation of MR parameters to histological features showed that NOE CEST and qMT imaging are sensitive to both acute and chronic injuries, whereas urea CEST shows a significant correlation only to acute injuries. CONCLUSION: These results indicate that our multiparametric approach allows comprehensive and totally noninvasive monitoring of renal function and histological changes for distinguishing different nephropathies.

Rapid whole-brain myelin imaging with selective inversion recovery and compressed SENSE.

PURPOSE: Quantitative magnetization transfer (QMT) using selective inversion recovery (SIR) can quantify the macromolecular-to-free proton pool size ratio (PSR), which has been shown to relate closely with myelin content. Currently clinical applications of SIR have been hampered by long scan times. In this work, the acceleration of SIR-QMT using CS-SENSE (compressed sensing SENSE) was systematically studied. THEORY AND METHODS: Phantoms of varied concentrations of bovine serum albumin and human scans were first conducted to evaluate the SNR, precision of SIR-QMT parameters, and scan time. Based on these results, an optimized CS-SENSE factor of 8 was determined and the test-retest repeatability was further investigated. RESULTS: A whole-brain SIR imaging of 6 min can be achieved. Bland-Altman analyses indicated excellent agreement between the test and retest sessions with a difference in mean PSR of 0.06% (and a difference in mean R1f of -0.001 s-1 ). In addition, the assessment of the intraclass correlation coefficient (ICC) revealed high reliability in nearly all the white matter and gray matter regions. In white matter regions, the ICC was 0.93 (95% confidence interval [CI]: 0.88-0.96, p < 0.001) for PSR, and 0.90 (95% CI: 0.83-0.94, p < 0.001) for R1f . In gray matter, ICC was 0.84 (95% CI: 0.66-0.93, p < 0.001) in PSR, and 0.98 (95% CI: 0.95-0.99, p < 0.001) for R1f . The method also showed excellent capability to detect focal lesions in multiple sclerosis. CONCLUSION: Rapid, reliable, and sensitive whole-brain SIR imaging can be achieved using CS-SENSE, which is expected to significantly promote widespread clinical translation.

Generalized Bloch model: A theory for pulsed magnetization transfer.

PURPOSE: The paper introduces a classical model to describe the dynamics of large spin-1/2 ensembles associated with nuclei bound in large molecule structures, commonly referred to as the semi-solid spin pool, and their magnetization transfer (MT) to spins of nuclei in water. THEORY AND METHODS: Like quantum-mechanical descriptions of spin dynamics and like the original Bloch equations, but unlike existing MT models, the proposed model is based on the algebra of angular momentum in the sense that it explicitly models the rotations induced by radiofrequency (RF) pulses. It generalizes the original Bloch model to non-exponential decays, which are, for example, observed for semi-solid spin pools. The combination of rotations with non-exponential decays is facilitated by describing the latter as Green's functions, comprised in an integro-differential equation. RESULTS: Our model describes the data of an inversion-recovery magnetization-transfer experiment with varying durations of the inversion pulse substantially better than established models. We made this observation for all measured data, but in particular for pulse durations smaller than 300 µs. Furthermore, we provide a linear approximation of the generalized Bloch model that reduces the simulation time by approximately a factor 15,000, enabling simulation of the spin dynamics caused by a rectangular RF-pulse in roughly 2 µs. CONCLUSION: The proposed theory unifies the original Bloch model, Henkelman's steady-state theory for MT, and the commonly assumed rotation induced by hard pulses (i.e., strong and infinitesimally short applications of RF-fields) and describes experimental data better than previous models.

Does the magnetization transfer effect bias chemical exchange saturation transfer effects? Quantifying chemical exchange saturation transfer in the presence of magnetization transfer.

PURPOSE: Chemical exchange saturation transfer (CEST) is an MRI technique sensitive to the presence of low-concentration solute protons exchanging with water. However, magnetization transfer (MT) effects also arise when large semisolid molecules interact with water, which biases CEST parameter estimates if quantitative models do not account for macromolecular effects. This study establishes under what conditions this bias is significant and demonstrates how using an appropriate model provides more accurate quantitative CEST measurements. METHODS: CEST and MT data were acquired in phantoms containing bovine serum albumin and agarose. Several quantitative CEST and MT models were used with the phantom data to demonstrate how underfitting can influence estimates of the CEST effect. CEST and MT data were acquired in healthy volunteers, and a two-pool model was fit in vivo and in vitro, whereas removing increasing amounts of CEST data to show biases in the CEST analysis also corrupts MT parameter estimates. RESULTS: When all significant CEST/MT effects were included, the derived parameter estimates for each CEST/MT pool significantly correlated (P < .05) with bovine serum albumin/agarose concentration; minimal or negative correlations were found with underfitted data. Additionally, a bootstrap analysis demonstrated that significant biases occur in MT parameter estimates (P < .001) when unmodeled CEST data are included in the analysis. CONCLUSIONS: These results indicate that current practices of simultaneously fitting both CEST and MT effects in model-based analyses can lead to significant bias in all parameter estimates unless a sufficiently detailed model is utilized. Therefore, care must be taken when quantifying CEST and MT effects in vivo by properly modeling data to minimize these biases.

Formalin tissue fixation biases myelin-sensitive MRI.

PURPOSE: Chemical fixatives such as formalin form cross-links between proteins and affect the relaxation times and diffusion properties of tissue. These fixation-induced changes likely also affect myelin density measurements produced by quantitative magnetization transfer and myelin water imaging. In this work, we evaluate these myelin-sensitive MRI methods for fixation-induced biases. METHODS: We perform quantitative magnetization transfer, myelin water imaging, and deuterium oxide-exchanged zero TE imaging on unfixed human spinal cord tissue at 9.4 Tesla and repeat these measurements after 1 day and 31 days of formalin fixation. RESULTS: The quantitative magnetization-transfer bound pool fraction increased by 30.7% ± 21.1% after 1 day of fixation and by 42.6% ± 33.9% after 31 days of fixation. Myelin water fraction increased by 39.7% ± 15.5% and 37.0% ± 15.9% at these same time points, and mean T2 of the myelin water pool nearly doubled. Reference-normalized deuterium oxide-exchanged zero TE signal intensity increased by 8.17% ± 6.03% after 31 days of fixation but did not change significantly after 1 day of fixation. After fixation, specimen cross-sectional area decreased by approximately 5%; after correction for shrinkage, changes in deuterium oxide-exchanged zero TE intensity were nearly eliminated. CONCLUSION: Bound pool fraction and myelin water fraction are significantly increased by formalin fixation, whereas deuterium oxide-exchanged zero TE intensity is minimally affected. Changes in quantitative magnetization transfer and myelin water imaging may be due in part to delamination and formation of vacuoles in the myelin sheath. Deuterium oxide-exchanged signal intensity may be altered by fixation-induced changes in myelin lipid solid-state 1 H T1 . We urge caution in the comparison of these measurements across subjects or specimens in different states, especially unfixed versus fixed tissue.

Assessment of renal fibrosis in murine diabetic nephropathy using quantitative magnetization transfer MRI.

PURPOSE: Renal fibrosis is a hallmark of progressive renal disease; however, current clinical tests are insufficient for assessing renal fibrosis. Here we evaluated the utility of quantitative magnetization transfer MRI in detecting renal fibrosis in a murine model of progressive diabetic nephropathy (DN). METHODS: The db/db eNOS-/- mice, a well-recognized model of progressive DN, and normal wild-type mice were imaged at 7T. The quantitative magnetization transfer data were collected in coronal plane using a 2D magnetization transfer prepared spoiled gradient echo sequence with a Gaussian-shaped presaturation pulse. Parameters were derived using a two-pool fitting model. A normal range of cortical pool size ratio (PSR) was defined as Mean±2SD of wild-type kidneys (N = 20). The cortical regions whose PSR values exceeded this threshold (threshold PSR) were assessed. The correlations between the PSR-based and histological (collagen IV or picrosirius red stain) fibrosis measurements were evaluated. RESULTS: Compared with wild-type mice, moderate increases in mean PSR values and scattered clusters of high PSR region were observed in cortex of DN mouse kidneys. Abnormally high PSR regions (% area) that were detected by the threshold PSR were significantly increased in renal cortexes of DN mice. These regions progressively increased on aging and highly correlated with histological fibrosis measures, while the mean PSR values correlated much less. CONCLUSION: Renal fibrosis in DN can be assessed by the quantitative magnetization transfer MRI and threshold analysis. This technique may be used as a novel imaging biomarker for DN and other renal diseases.

Glioblastoma (GBM) effects on quantitative MRI of contralateral normal appearing white matter.

PURPOSE: The objective was to investigate (with quantitative MRI) whether the normal appearing white matter (NAWM) of glioblastoma (GBM) patients on the contralateral side (cNAWM) was different from NAWM of healthy controls. METHODS: Thirteen patients with newly diagnosed GBM and nine healthy age-matched controls were MRI-scanned with quantitative magnetization transfer (qMT), chemical exchange saturation transfer (CEST), and transverse relaxation time (T2)-mapping. MRI scans were performed after surgery and before chemo-radiation treatment. Comprehensive qMT, CEST, T2 data were acquired. A two-pool MT model was fit to qMT data in transient state, to calculate MT model parameters [Formula: see text]. CEST signal was isolated by removing the contributions from the MT and direct water saturation, and CEST signal was calculated for Amide (CESTAmide), Amine (CESTAmine) and nuclear overhauser effect, NOE (CESTNOE). RESULTS: There was no difference between GBM patients and normal controls in the qMT properties of the macromolecular pool [Formula: see text]. However, their free water pool spectrum was different (1/RaT2a,patient = 28.1 ± 3.9, 1/RaT2a,control = 25.0 ± 1.1, p = 0.03). This difference could be attributed to the difference in their T2 time ([Formula: see text] = 83 ± 4, [Formula: see text] = 88 ± 1, p = 0.004). CEST signals were statistically significantly different with the CESTAmide having the largest difference between the two cohorts (CESTAmide,patient = 2.8 ± 0.4, CESTAmide,control = 3.4 ± 0.5, p = 0.009). CONCLUSIONS: CEST in cNAWM of GBM patients was lower than healthy controls which could be caused by modified brain metabolism due to tumor cell infiltration. There was no difference in MT properties of the patients and controls, however, the differences in free water pool properties were mainly due to reduced T2 in cNAWM of the patients (resulting from structural changes and increased cellularity).

Incorporating dixon multi-echo fat water separation for novel quantitative magnetization transfer of the human optic nerve in vivo.

PURPOSE: The optic nerve (ON) represents the sole pathway between the eyes and brain; consequently, diseases of the ON can have dramatic effects on vision. However, quantitative magnetization transfer (qMT) applications in the ON have been limited to ex vivo studies, in part because of the fatty connective tissue that surrounds the ON, confounding the magnetization transfer (MT) experiment. Therefore, the aim of this study was to implement a multi-echo Dixon fat-water separation approach to remove the fat component from MT images. METHODS: MT measurements were taken in a single slice of the ON and frontal lobe using a three-echo Dixon readout, and the water and out-of-phase images were applied to a two-pool model in ON tissue and brain white matter to evaluate the effectiveness of using Dixon fat-water separation to remove fatty tissue from MT images. RESULTS: White matter data showed no significant differences between image types; however, there was a significant increase (p < 0.05) in variation in the out-of-phase images in the ON relative to the water images. CONCLUSIONS: The results of this study demonstrate that Dixon fat-water separation can be robustly used for accurate MT quantification of anatomies susceptible to partial volume effects resulting from fat. Magn Reson Med 77:707-716, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

On-resonance variable delay multipulse scheme for imaging of fast-exchanging protons and semisolid macromolecules.

PURPOSE: To develop an on-resonance variable delay multipulse (VDMP) scheme to image magnetization transfer contrast (MTC) and the chemical exchange saturation transfer (CEST) contrast of total fast-exchanging protons (TFP) with exchange rate above approximately 1 kHz. METHODS: A train of high power binomial pulses was applied at the water resonance. The interpulse delay, called mixing time, was varied to observe its effect on the water signal reduction, allowing separation and quantification of MTC and CEST contributions as a result of their different proton transfer rates. The fast-exchanging protons in CEST and MTC are labeled together with the short T2 components in MTC and separated out using a variable mixing time. RESULTS: Phantom studies of selected metabolite solutions (glucose, glutamate, creatine, myo-inositol), bovine serum albumin (BSA), and hair conditioner show the capability of on-resonance VDMP to separate out exchangeable protons with exchange rates above 1 kHz. Quantitative MTC and TFP maps were acquired on healthy mouse brains using this method, showing strong gray/white matter contrast for the slowly transferring MTC protons, whereas the TFP map was more uniform across the brain but somewhat higher in gray matter. CONCLUSIONS: The new method provides a simple way of imaging fast-exchanging protons and MTC components with a slow transfer rate. Magn Reson Med 77:730-739, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Influence of water compartmentation and heterogeneous relaxation on quantitative magnetization transfer imaging in rodent brain tumors.

PURPOSE: The goal of this study was to investigate the influence of water compartmentation and heterogeneous relaxation properties on quantitative magnetization transfer (qMT) imaging in tissues, and in particular whether a two-pool model is sufficient to describe qMT data in brain tumors. METHODS: Computer simulations and in vivo experiments with a series of qMT measurements before and after injection of Gd-DTPA were performed. Both off-resonance pulsed saturation (pulsed) and on-resonance selective inversion recovery (SIR) qMT methods were used, and all data were fit with a two-pool model only. RESULTS: Simulations indicated that a two-pool fitting of four-pool data yielded accurate measures of pool size ratio (PSR) of macromolecular versus free water protons when there were fast transcytolemmal exchange and slow R1 recovery. The fitted in vivo PSR of both pulsed and SIR qMT methods showed no dependence on R1 variations caused by different concentrations of Gd-DTPA during wash-out, whereas the fitted kex (magnetization transfer exchange rate) changed significantly with R1 . CONCLUSION: A two-pool model provides reproducible estimates of PSR in brain tumors independent of relaxation properties in the presence of relatively fast transcytolemmal exchange, whereas estimates of kex are biased by relaxation variations. In addition, estimates of PSR in brain tumors using the pulsed and SIR qMT methods agree well with one another. Magn Reson Med 76:635-644, 2016. © 2015 Wiley Periodicals, Inc.

Longitudinal assessment of spinal cord injuries in nonhuman primates with quantitative magnetization transfer.

PURPOSE: This study aimed to evaluate the reproducibility and specificity of quantitative magnetization transfer (qMT) imaging for monitoring spinal cord injuries (SCIs). METHODS: MRI scans were performed in anesthetized monkeys at 9.4T, before and serially after a unilateral lesion of the cervical spinal cord. A two-pool fitting model was used to derive qMT parameters. RESULTS: qMT measures were reproducible across normal subjects, with an average pool size ratio (PSR) of 0.086 ± 0.003 (mean ± SD) for gray matter, and 0.120 ± 0.005 for white matter, respectively. Compared with normal gray matter, the PSR of abnormal tissues rostral and caudal to the injury site decreased by 19.5% (P < 0.05), while the PSR of the cyst-like volume decreased drastically weeks after SCI. Strong correlations in cyst-like regions were observed between PSR and other MRI measures including longitudinal relaxation rate (R1 ), apparent diffusion coefficient and fractional anisotropy (FA). Decreased PSR and FA values correlated well with demyelination in abnormal tissues. CONCLUSION: The qMT parameters provide robust and specific information about the molecular and cellular changes produced by SCI. PSR detected demyelination and loss of macromolecules in abnormal tissue regions rostral and caudal to the cyst/lesion sites.

In vivo quantitative magnetization transfer imaging correlates with histology during de- and remyelination in cuprizone-treated mice.

The pool size ratio measured by quantitative magnetization transfer MRI is hypothesized to closely reflect myelin density, but their relationship has so far been confirmed mostly in ex vivo conditions. We investigate the correspondence between this parameter measured in vivo at 7.0 T, with Black Gold II staining for myelin fibres, and with myelin basic protein and beta-tubulin immunofluorescence in a hybrid longitudinal study of C57BL/6 and SJL/J mice treated with cuprizone, a neurotoxicant causing relatively selective myelin loss followed by spontaneous remyelination upon treatment suspension. Our results confirm that pool size ratio measurements correlate with myelin content, with the correlation coefficient depending on strain and staining method, and demonstrate the in vivo applicability of this MRI technique to experimental mouse models of multiple sclerosis.

Investigating balance-related gait patterns and their relationship with maximum torques generated by the hamstrings and quadriceps in older adults - Results from the Baltimore longitudinal study of aging.

BACKGROUND: Balance-related gait patterns in older adults can be objectively discerned through the examination of gait parameters, maximum leg torques, and their interconnections. OBJECTIVE: To investigate the correlation between leg muscle strength and balance during gait concerning functional performance in healthy older adults. METHODS: Participants included 117 adults aged 60-95 years were recruited from the Baltimore Longitudinal Study of Aging (BLSA). They underwent evaluations of gait, balance, and maximum isometric leg torque (for both hamstrings and quadriceps). Analyses examined the association between leg torque and functional performance among those with higher and lower balances. RESULTS: Individuals with lower balance (n = 43) were older, more prone to experiencing a fear of falling, and exhibited lower functional performance (gait speeds and Generalized Gait Stability Scores (GGSS), ps < 0.001) compared to their counterparts with higher balance (n = 74). At a usual walking pace, the GGSS showed a positive association with concentric Quadriceps Maximum Torque (QMT) in participants with lower balance (p = 0.013). Conversely, it displayed a positive association with eccentric QMT in those with higher balance (p = 0.014). At a fast walking pace, only individuals with higher balance demonstrated a positive muscle torque association with both gait speed and GGSS, encompassing concentric and eccentric actions in both the quadriceps and hamstrings (ps < 0.050). CONCLUSION: Evaluating muscle strength capacity in both concentric and eccentric phases during dynamic high-effort events, along with investigating their associations with gait performance, can be beneficial for identifying subtle gait deficits. This comprehensive approach may assist in the early detection of gait deterioration among healthy older adults, given the intricate muscle activations involved in lower body functional performance.

Rapid whole-brain quantitative MT imaging.

PURPOSE: To provide a robust whole-brain quantitative magnetization transfer (MT) imaging method that is not limited by long acquisition times. METHODS: Two variants of a spiral 2D interleaved multi-slice spoiled gradient echo (SPGR) sequence are used for rapid quantitative MT imaging of the brain at 3 T. A dual flip angle, steady-state prepared, double-contrast method is used for combined B1 and-T1 mapping in combination with a single-contrast MT-prepared acquisition over a range of different saturation flip angles (50 deg to 850 deg) and offset frequencies (1 kHz and 10 kHz). Five sets (containing minimum 6 to maximum 18 scans) with different MT-weightings were acquired. In addition, main magnetic field inhomogeneities (ΔB0) were measured from two Cartesian low-resolution 2D SPGR scans with different echo times. Quantitative MT model parameters were derived from all sets using a two-pool continuous-wave model analysis, yielding the pool-size ratio, F, their exchange rate, kf, and their transverse relaxation time, T2r. RESULTS: Whole-brain quantitative MT imaging was feasible for all sets with total acquisition times ranging from 7:15 min down to 3:15 min. For accurate modeling, B1-correction was essential for all investigated sets, whereas ΔB0-correction showed limited bias for the observed maximum off-resonances at 3 T. CONCLUSION: The combination of rapid B1-T1 mapping and MT-weighted imaging using a 2D multi-slice spiral SPGR research sequence offers excellent prospects for rapid whole-brain quantitative MT imaging in the clinical setting.

Quadrato motor training (QMT) influences IL-1ß expression and creativity: Implications for inflammatory state reduction and cognitive enhancement.

Mind-body practices and meditation have been increasingly studied in recent years due to their beneficial effects on cognition, and physical and psychological health. Growing evidence suggests that these practices could be utilized as interventions to impact age-related biological processes, such as cognitive decline, inflammation, and homeostatic dysregulation. Indeed, it has been reported that mindful meditation may induce neuroplasticity in brain regions involved in control of attention, emotional regulation, and self-awareness. In the current research we studied the effects of a recently developed movement meditation, named the Quadrato Motor Training (QMT), on the proinflammatory cytokine Interleukin-1beta (IL-1ß), utilizing a pre-post design. In addition to its role in the immune system, IL-1ß is also an important mediator of neuroimmune responses related to sickness behavior, and plays a role in complex cognitive processes, such as synaptic plasticity, neurogenesis, and neuromodulation. Thirty healthy participants were divided in two groups, one performing QMT for 2 months, and one passive control group. Salivary IL-1ß expression was examined by ELISA to measure protein levels and by qRT-PCR to quantify mRNA. In addition, the methylation profile of the IL-1ß promoter was examined. All participants further conducted the Alternate Uses Task (AUT) and Hidden Figure Test (HFT), to measure their creativity and spatial cognition. The results showed that, following QMT practice, IL-1ß protein level decreased and creativity increased, compared to the control group. These data demonstrate that QMT may help reduce inflammatory states and promote cognitive improvement, highlighting the importance of non-pharmacological approaches to health and well-being.

Longitudinal multiparametric MRI of traumatic spinal cord injury in animal models.

Multi-parametric MRI (mpMRI) technology enables non-invasive and quantitative assessments of the structural, molecular, and functional characteristics of various neurological diseases. Despite the recognized importance of studying spinal cord pathology, mpMRI applications in spinal cord research have been somewhat limited, partly due to technical challenges associated with spine imaging. However, advances in imaging techniques and improved image quality now allow longitudinal investigations of a comprehensive range of spinal cord pathological features by exploiting different endogenous MRI contrasts. This review summarizes the use of mpMRI techniques including blood oxygenation level-dependent (BOLD) functional MRI (fMRI), diffusion tensor imaging (DTI), quantitative magnetization transfer (qMT), and chemical exchange saturation transfer (CEST) MRI in monitoring different aspects of spinal cord pathology. These aspects include cyst formation and axonal disruption, demyelination and remyelination, changes in the excitability of spinal grey matter and the integrity of intrinsic functional circuits, and non-specific molecular changes associated with secondary injury and neuroinflammation. These approaches are illustrated with reference to a nonhuman primate (NHP) model of traumatic cervical spinal cord injuries (SCI). We highlight the benefits of using NHP SCI models to guide future studies of human spinal cord pathology, and demonstrate how mpMRI can capture distinctive features of spinal cord pathology that were previously inaccessible. Furthermore, the development of mechanism-based MRI biomarkers from mpMRI studies can provide clinically useful imaging indices for understanding the mechanisms by which injured spinal cords progress and repair. These biomarkers can assist in the diagnosis, prognosis, and evaluation of therapies for SCI patients, potentially leading to improved outcomes.

Lesion distribution and substrate of white matter damage in myotonic dystrophy type 1: Comparison with multiple sclerosis.

Myotonic Dystrophy type 1 (DM1) is an autosomal dominant condition caused by expansion of the CTG triplet repeats within the myotonic dystrophy protein of the kinase (DMPK) gene. The central nervous system is involved in the disease, with multiple symptoms including cognitive impairment. A typical feature of DM1 is the presence of widespread white matter (WM) lesions, whose total volume is associated with CTG triplet expansion. The aim of this study was to characterize the distribution and pathological substrate of these lesions as well as the normal appearing WM (NAWM) using quantitative magnetization transfer (qMT) MRI, and comparing data from DM1 patients with those from patients with multiple sclerosis (MS). Twenty-eight patients with DM1, 29 patients with relapsing-remitting MS, and 15 healthy controls had an MRI scan, including conventional and qMT imaging. The average pool size ratio (F), a proxy of myelination, was computed within lesions and NAWM for every participant. The lesion masks were warped into MNI space and lesion probability maps were obtained for each patient group. The lesion distribution, total lesion load and the tissue-specific mean F were compared between groups. The supratentorial distribution of lesions was similar in the 2 patient groups, although mean lesion volume was higher in MS than DM1. DM1 presented higher prevalence of anterior temporal lobe lesions, but none in the cerebellum and brainstem. Significantly reduced F values were found within DM1 lesions, suggesting a loss of myelin density. While F was reduced in the NAWM of MS patients, it did not differ between DM1 and controls. Our results provide further evidence for a need to compare histology and imaging using new MRI techniques in DM1 patients, in order to further our understanding of the underlying disease process contributing to WM disease.

Advanced Imaging of Brain Metastases: From Augmenting Visualization and Improving Diagnosis to Evaluating Treatment Response.

Early detection of brain metastases and differentiation from other neuropathologies is crucial. Although biopsy is often required for definitive diagnosis, imaging can provide useful information. After treatment commences, imaging is also performed to assess the efficacy of treatment. Contrast-enhanced magnetic resonance imaging (MRI) is the traditional imaging method for the evaluation of brain metastases, as it provides information about lesion size, morphology, and macroscopic properties. Newer MRI sequences have been developed to increase the conspicuity of detecting enhancing metastases. Other advanced MRI techniques, that have the capability to probe beyond the anatomic structure, are available to characterize micro-structures, cellularity, physiology, perfusion, and metabolism. Artificial intelligence provides powerful computational tools for detection, segmentation, classification, prediction, and prognosis. We highlight and review a few advanced MRI techniques for the assessment of brain metastases-specifically for (1) diagnosis, including differentiating between malignancy types and (2) evaluation of treatment response, including the differentiation between radiation necrosis and disease progression.