Magnetization Transfer Ratio Research Articles

Spectrally selective and interleaved water imaging and fat imaging (siWIFI).

To develop a novel imaging sequence that independently acquires water and fat images while being inherently insensitive to motion. The new sequence, termed spectrally selective and interleaved water imaging and fat imaging (siWIFI), uses a narrow bandwidth RF pulse for selective excitation of water and fat separately. The interleaved acquisition method ensures that the obtained water and fat images are inherently coregistered. A radial sampling strategy further reduces motion-induced artifacts. Phantoms with lipid concentrations ranging from 0% to 50% were scanned to measure fat fraction. Moreover, healthy volunteers were scanned to assess the in vivo feasibility of fat fraction measurement at the hip, knee, and liver. In vivo fat fraction measurements were compared with those from vendor-provided iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) scans. Furthermore, a magnetization transfer (MT) preparation module was incorporated to demonstrate the feasibility of simultaneous measurement of fat fraction and MT ratio utilizing the siWIFI framework. The phantom fat fractions measured by siWIFI showed excellent correlation with lipid concentrations (R2 = 0.9995, p < 0.0001). In vivo studies demonstrated that the fat fractions obtained from siWIFI were comparable to those from IDEAL. Additionally, siWIFI demonstrates reduced motion artifacts from pulsatile flow in knee imaging compared to IDEAL scans and exhibits less sensitivity to respiratory motion in liver imaging compared to IDEAL scans without breath-hold. The knee imaging study demonstrated that MT-prepared siWIFI is capable of generating fat fraction and MT ratio maps simultaneously. The proposed siWIFI sequence allows selective water-fat imaging and quantification with reduced motion artifacts.

Amide proton transfer-weighted CEST MRI for radiotherapy target delineation of glioblastoma: a prospective pilot study

BackgroundExtensive glioblastoma infiltration justifies a 15-mm margin around the gross tumor volume (GTV) to define the radiotherapy clinical target volume (CTV). Amide proton transfer (APT)-weighted imaging could enable visualization of tumor infiltration, allowing more accurate GTV delineation. We quantified the impact of integrating APT-weighted imaging into GTV delineation of glioblastoma and compared two APT-weighted quantification methods—magnetization transfer ratio asymmetry (MTRasym) and Lorentzian difference (LD) analysis—for target delineation.MethodsNine glioblastoma patients underwent an extended imaging protocol prior to radiotherapy, yielding APT-weighted MTRasym and LD maps. From both maps, biological tumor volumes were generated (BTVMTRasym and BTVLD) and added to the conventional GTV to generate biological GTVs (GTVbio,MTRasym and GTVbio,LD). Wilcoxon signed-rank tests were performed for comparisons.ResultsThe GTVbio,MTRasym and GTVbio,LD were significantly larger than the conventional GTV (p ≤ 0.022), with a median volume increase of 9.3% and 2.1%, respectively. The GTVbio,MTRasym and GTVbio,LD were significantly smaller than the CTV (p = 0.004), with a median volume reduction of 72.1% and 70.9%, respectively. There was no significant volume difference between the BTVMTRasym and BTVLD (p = 0.074). In three patients, BTVMTRasym delineation was affected by elevated signals at the brain periphery due to residual motion artifacts; this elevation was absent on the APT-weighted LD maps.ConclusionLarger biological GTVs compared to the conventional GTV highlight the potential of APT-weighted imaging for radiotherapy target delineation of glioblastoma. APT-weighted LD mapping may be advantageous for target delineation as it may be more robust against motion artifacts.Relevance statementThe introduction of APT-weighted imaging may, ultimately, enhance visualization of tumor infiltration and eliminate the need for the substantial 15-mm safety margin for target delineation of glioblastoma. This could reduce the risk of radiation toxicity while still effectively irradiating the tumor.Trial registrationNCT05970757 (ClinicalTrials.gov).Key PointsIntegration of APT-weighted imaging into target delineation for radiotherapy is feasible.The integration of APT-weighted imaging yields larger GTVs in glioblastoma.APT-weighted LD mapping may be more robust against motion artifacts than APT-weighted MTRasym.Graphical

Saturation transfer (CEST and MT) MRI for characterization of U-87 MG glioma in the rat.

The focus of this work was to identify the optimal magnetic resonance imaging (MRI) contrast between orthotopic U-87 MG tumours and normal appearing brain with the eventual goal of treatment response monitoring. U-87 MG human glioblastoma cells were injected into the brain of RNU nude rats (n= 9). The rats were imaged at 7T at three timepoints for all animals: 3-5, 7-9, and 11-13 days after implantation. Whole-brain T1-weighted (before and after gadolinium contrast agent injection), diffusion, and fluid-attenuated inversion recovery scans were performed. In addition, single-slice saturation-transfer-weighted chemical exchange saturation transfer (CEST), magnetization transfer (MT), and water saturation shift referencing (WASSR) contrast Z-spectra and T1 and T2 maps were also acquired. The MT and WASSR Z-spectra and T1 map were fitted to a two-pool quantitative MT model to estimate the T2 of the free and macromolecular-bound water molecules, the relative macromolecular pool size (M0, MT), and the magnetization exchange rate from the macromolecular pool to the free pool (RMT). The T1-corrected apparent exchange-dependent relaxation (AREX) metric to isolate the CEST contributions was also calculated. The lesion on M0, MT and AREX maps with a B1 of 2μT best matched the hyperintensity on the post-contrast T1-weighted image. There was also good separation in Z-spectra between the lesion and contralateral cortex in the 2-μT CEST and 3- and 5-μT MT Z-spectra at all time points. A pairwise Wilcoxon signed-rank tests with Holm-Bonferroni adjustment on MRI parameters was performed and the differences between enhancing lesion and contralateral cortex for the MT ratio with 2μT saturation at 3.6ppm frequency offset (corresponding to the amide chemical group) and M0, MT were both strongly significant (p< 0.001) at all time points. This work has identified that differences between enhancing lesion and contralateral cortex are strongest in MTR with B1=2μT at 3.6ppm and relative macromolecular pool size (M0, MT) images over entire period of 3-13 days after cancer cell implantation.

Diffusion kurtosis imaging, MAP-MRI and NODDI can selectively track gray matter myelin density in the primate cerebral cortex

Abstract Diffusion magnetic resonance imaging (dMRI) has been widely used to model the trajectory of myelinated fiber bundles in the white matter. Increasingly, it is also used to evaluate the microstructure of the cerebral cortex gray matter. For example, in diffusion tensor imaging (DTI) of the cortex, fractional anisotropy (FA) correlates strongly with the anisotropy of cellular anatomy, while radial diffusivity (RD) tracks the anisotropy of myelinated fibers. However, no DTI parameter shows specificity to gray matter myelin density. Here we show that three higher order diffusion parameters - the mean diffusion kurtosis (MK), the Neurite Density Index (NDI) from NODDI, and the Non-Gaussian (NG) parameter from MAP-MRI— each track the laminar and regional myelin density of the primate cerebral cortex in fine detail. We carried out ultra-high resolution, multi-shelled dMRI in ex-vivo marmoset monkey brains. We compared the spatial mapping of the MK, NDI, and ND diffusion parameters to the cortical myelin distribution of these brains, with the latter obtained in two ways: First, using histological sections finely co-registered to the MRI, and second using magnetization transfer ratio MRI scans (MTR), an established non-diffusion method for imaging myelin density. We found that, in contrast to DTI parameters, each of these higher order diffusion measures captured the spatial variation of myelin density in the cortex. The demonstration that diffusion parameters exhibit both sensitivity and specificity for gray matter myelin density will allow dMRI to more effectively track human disease, in which myelinated and non-myelinated tissue compartments are affected differentially.

Reproducibility of 3D chemical exchange saturation transfer (CEST) contrasts in the healthy brain at 3T

Chemical exchange saturation transfer (CEST) imaging may provide novel contrast for the diagnosis, prognosis, and monitoring of the progression or treatment of neurological applications. However, the reproducibility of prominent CEST contrasts like amide CEST and nuclear Overhauser enhancement (NOE) CEST must be characterized in healthy brain gray matter (GM) and white matter (GM) prior to clinical implementation. The objective of this study was to characterize the reproducibility of four different CEST contrasts in the healthy human brain. Using a 3T MRI scanner, two 3D CEST scans were acquired in 12 healthy subjects (7 females, mean age (± SD) 26 ± 4 years) approximately 10 days apart. Scan-rescan reproducibility was measured for four contrasts: amine/amide concentration-independent detection (AACID), Amide*, and inverse magnetization transfer ratio (MTRRex) contrast for amide and NOE. Reproducibility was evaluated between- and within-subjects using coefficients of variation (CV) and the percent difference between measurements. AACID and NOE-MTRRex contrasts demonstrated the lowest within-subject CVs (0.8–1.2% and 1.6-2.0%, respectively), between-subject CVs (1.2–2.1% and 3.4–4.2%, respectively), and percent difference (1.2–1.4% and 2.2–2.8%, respectively) for both GM and WM. AACID and NOE-MTRRex contrasts demonstrated the highest reproducibility and represented stable measurements suitable for characterizing changes in brain tissue caused by pathological processes.

Toward quantitative CEST imaging of glutamate in the mouse brain using a multi-pool exchange model calibrated by 1H-MRS.

To develop a CEST quantification model to map glutamate concentration in the mouse brain at 11.7 T, overcoming the limitations of conventional glutamate-weighted CEST (gluCEST) contrast (magnetization transfer ratio with asymmetric analysis). 1H-MRS was used as a gold standard for glutamate quantification to calibrate a CEST-based quantitative pipeline. Joint localized measurements of Z-spectra at B1 = 5 μT and quantitative 1H-MRS were carried out in two voxels of interest in the mouse brain. A six-pool Bloch-McConnell model was found appropriate to fit experimental data. Glutamate exchange rate was estimated in both regions with this dedicated multi-pool fitting model and using glutamate concentration determined by 1H-MRS. Glutamate exchange rate was estimated to be ˜1300 Hz in the mouse brain. Using this calibrated value, maps of glutamate concentration in the mouse brain were obtained by pixel-by-pixel fitting of Z-spectra at B1 = 5 μT. A complementary study of simulations, however, showed that the quantitative model has high sensitivity to noise, and therefore, requires high-SNR acquisitions. Interestingly, fitted [Glu] seemed to be overestimated compared to 1H-MRS measurements, although it was estimated with simulations that the model has no intrinsic fitting bias with our experimental level of noise. The hypothesis of an unknown proton-exchanging pool contributing to gluCEST signal is discussed. High-resolution mapping of glutamate in the brain was made possible using the proposed calibrated quantification model of gluCEST data. Further studying of the in vivo molecular contributions to gluCEST signal could improve modeling.

Tract-specific magnetization transfer ratio provides insights into the severity of degenerative cervical myelopathy.

Cross-sectional study. This study's goal is to report whether Magnetization Transfer Ratio (MTR) can evaluate the severity of white matter (WM) injury in degenerative cervical myelopathy (DCM). Laureate Institute of Brain Research, USA; Department of Neurosurgery, University of Oklahoma Health Sciences Center, USA. 27 DCM patients were aged-matched with 20 healthy controls (HC) and categorized into treatment groups based on modified Japanese Orthopedic Association (mJOA) severity (11 mild and 16 moderate/severe). Regional and tract MTRs were extracted from the two vertebral levels containing maximum compression within magnetization transfer images. MTR differences between groups were assessed using a one-way ANOVA or Kruskal-Wallis test. The association between MTR and mJOA measures was evaluated using Spearman's correlation. Significant decreases in MTR were found between HC and moderate/severe groups in the overall (p = 0.0065) and ventral (p = 0.0009) WM regions; and ventral corticospinal (p = 0.0101), ventral reticulospinal (p = 0.0084), spinal lemniscus (p = 0.0079), and fasciculus cuneatus (p = 0.0219) tracts. The spinal lemniscus MTR also significantly decreased between HC and mild groups (p = 0.038). Ventral reticulospinal tract MTR correlated with upper (r = 0.439; p = 0.022) and lower (r = 0.386; p = 0.047) limb motor mJOA scores. Significant tract-based MTR changes and correlations align with known DCM symptoms, are demonstrated to be lost at the regional level, and display the inhomogeneous compressive damage occurring within DCM spinal cords.

Utility of dual-energy CT and advanced multiparametric MRI based imaging biomarkers of pancreatic fibrosis in grading the severity of chronic pancreatitis.

To non-invasively quantify pancreatic fibrosis and grade severity of chronic pancreatitis (CP) on dual-energy CT (DECT) and multiparametric MRI (mpMRI). We included 72 patients (mean age:30years; 59 men) with suspected or confirmed CP from December 2019 to December 2021 graded as equivocal(n = 20), mild(n = 18), and moderate-marked(n = 34) using composite imaging and endoscopic ultrasound criteria. Study patients underwent multiphasic DECT and mpMRI of the abdomen. Normalized iodine concentration(NIC) and fat fraction(FF) on 6-minute delayed DECT, and T1 relaxation time(T1Rt), extracellular volume fraction(ECVf), intravoxel incoherent motion-based perfusion fraction(PF), and magnetization transfer ratio(MTR) on mpMRI of pancreas were compared. 20 renal donors(for DECT) and 20 patients with renal mass(for mpMRI) served as controls. NIC of pancreas in controls and progressive grades of CP were 0.24 ± 0.05, 0.80 ± 0.18, 1.06 ± 0.23, 1.40 ± 0.36, FF were 9.28 ± 5.89, 14.19 ± 5.29, 17.31 ± 5.99, 29.32 ± 12.22, T1Rt were 590.11 ± 61.13, 801.93 ± 211.01, 1006.79 ± 352.18, 1388.01 ± 312.23ms, ECVf were 0.07 ± 0.03, 0.30 ± 0.12, 0.41 ± 0.12, 0.53 ± 0.13, PF were 0.38 ± 0.04, 0.28 ± 0.07, 0.25 ± 0.09, 0.21 ± 0.05 and MTR were 0.12 ± 0.03, 0.15 ± 0.06, 0.21 ± 0.07, 0.26 ± 0.06, respectively. There were significant differences for all quantitative parameters between controls and mild CP; for NIC, PF, and ECVf between controls and progressive CP grades (p < 0.05). Area under curve for NIC, FF, T1Rt, ECVf, PF, and MTR in differentiating controls and mild CP were 1.00, 0.86, 0.95, 1.00, 0.90 and 0.84 respectively and for NIC, FF, ECVf and PF in differentiating controls and equivocal CP were 1.00, 0.76, 0.95 and 0.92 respectively. DECT and mpMRI were useful in quantifying pancreatic fibrosis and grading the severity of CP. NIC was the most accurate marker.

Magnetization transfer MRI of intragastric milk digestion: A feasibility study in humans

Gastric milk protein coagulation has been extensively studied using in vitro and animal models. Yet, verifying these results in humans remains essential. In this study, we assessed the feasibility of using MT MRI for monitoring milk protein coagulation in vivo in humans. Twelve adults underwent MRI scans before and after ingesting 300 g of milk with low- or high-protein denaturation (LPD or HPD, respectively). We assessed coagulation and gastric emptying dynamics by deriving the MT ratio (MTR), total gastric content (TGC), semi-solid, and liquid volumes. The MTR values increased during digestion for both milk products, indicating an increase in the degree of coagulation. Prolonged heating of milk did not affect the MTR (MD = 16 %, 95 % CI [10–21], p = 0.15), but resulted in higher TGC volumes (MD 40.3 mL, 95 % CI [25.5–55.1], p = 0.044), indicating slower gastric emptying. We thus showed that by combining MT with conventional anatomical MRI both milk protein coagulation and gastric emptying dynamics, and thereby the impact of heating on gastric milk digestion, can be assessed in vivo in humans. Our work underpins the feasibility of using MRI as a non-invasive imaging tool for studying the effects of food processing and composition on gastric digestion.

Unsupervised Pattern Analysis to Differentiate Multiple Sclerosis Phenotypes Using Principal Component Analysis on Various MRI Sequences.

Background: Multiple sclerosis (MS) has two main phenotypes: relapse-remitting MS (RRMS) and progressive MS (PMS), distinguished by disability profiles and treatment response. Differentiating them using conventional MRI is challenging. Objective: This study explores the use of scaled subprofile modelling using principal component analysis (SSM/PCA) on MRI data to distinguish between MS phenotypes. Methods: MRI scans were performed on patients with RRMS (n = 30) and patients with PMS (n = 20), using the standard sequences T1w, T2w, T2w-FLAIR, and the myelin-sensitive sequences magnetisation transfer (MT) ratio (MTR), quantitative MT (qMT), inhomogeneous MT ratio (ihMTR), and quantitative inhomogeneous MT (qihMT). Results: SSM/PCA analysis of qihMT images best differentiated PMS from RRMS, with the highest specificity (87%) and positive predictive value (PPV) (83%), but a lower sensitivity (67%) and negative predictive value (NPV) (72%). Conversely, T1w data analysis showed the highest sensitivity (93%) and NPV (89%), with a lower PPV (67%) and specificity (53%). Phenotype classification agreement between T1w and qihMT was observed in 57% of patients. In the subset with concordant classifications, the sensitivity, specificity, PPV, and NPV were 100%, 88%, 90%, and 100%, respectively. Conclusions: SSM/PCA on MRI data revealed distinctive patterns for MS phenotypes. Optimal discrimination occurred with qihMT and T1w sequences, with qihMT identifying PMS and T1w identifying RRMS. When qihMT and T1w analyses align, MS phenotype prediction improves.

Longitudinal Imaging of Injured Spinal Cord Myelin and White Matter with 3D Ultrashort Echo Time Magnetization Transfer (UTE-MT) and Diffusion MRI.

Quantitative MRI techniques could be helpful to noninvasively and longitudinally monitor dynamic changes in spinal cord white matter following injury, but imaging and postprocessing techniques in small animals remain lacking. Unilateral C5 hemisection lesions were created in a rat model, and ultrashort echo time magnetization transfer (UTE-MT) and diffusion-weighted sequences were used for imaging following injury. Magnetization transfer ratio (MTR) measurements and preferential diffusion along the longitudinal axis of the spinal cord were calculated as fractional anisotropy or an apparent diffusion coefficient ratio over transverse directions. The area of myelinated white matter was obtained by thresholding the spinal cord using mean MTR or diffusion ratio values from the contralesional side of the spinal cord. A decrease in white matter areas was observed on the ipsilesional side caudal to the lesions, which is consistent with known myelin and axonal changes following spinal cord injury. The myelinated white matter area obtained through the UTE-MT technique and the white matter area obtained through diffusion imaging techniques showed better performance to distinguish evolution after injury (AUCs > 0.94, p < 0.001) than the mean MTR (AUC = 0.74, p = 0.01) or ADC ratio (AUC = 0.68, p = 0.05) values themselves. Immunostaining for myelin basic protein (MBP) and neurofilament protein NF200 (NF200) showed atrophy and axonal degeneration, confirming the MRI results. These compositional and microstructural MRI techniques may be used to detect demyelination or remyelination in the spinal cord after spinal cord injury.

Significant age-related differences between lower leg muscles of older and younger female subjects detected by ultrashort echo time magnetization transfer modeling.

Magnetization transfer (MT) magnetic resonance imaging (MRI) can be used to estimate the fraction of water and macromolecular proton pools in tissues. MT modeling paired with ultrashort echo time acquisition (UTE-MT modeling) has been proposed to improve the evaluation of the myotendinous junction and fibrosis in muscle tissues, which the latter increases with aging. This study aimed to determine if the UTE-MT modeling technique is sensitive to age-related changes in the skeletal muscles of the lower leg. Institutional review board approval was obtained, and all recruited subjects provided written informed consent. The legs of 31 healthy younger (28.1±6.1years old, BMI = 22.3±3.5) and 20 older (74.7±5.5years old, BMI = 26.7±5.9) female subjects were imaged using UTE sequences on a 3T MRI scanner. MT ratio (MTR), macromolecular fraction (MMF), macromolecular T2 (T2-MM), and water T2 (T2-W) were calculated using UTE-MT modeling for the anterior tibialis (ATM), posterior tibialis (PTM), soleus (SM), and combined lateral muscles. Results were compared between groups using the Wilcoxon rank sum test. Three independent observers selected regions of interest (ROIs) and processed UTE-MRI images separately, and the intraclass correlation coefficient (ICC) was calculated for a reproducibility study. Significantly lower mean MTR and MMF values were present in the older compared with the younger group in all studied lower leg muscles. T2-MM showed significantly lower values in the older group only for PTM and SM muscles. In contrast, T2-W showed significantly higher values in the older group. The age-related differences were more pronounced for MMF (-17 to -19%) and T2-W (+20 to 47%) measurements in all muscle groups compared with other investigated MR measures. ICCs were higher than 0.93, indicating excellent consistency between the ROI selection and MRI measurements of independent readers. As demonstrated by significant differences between younger and older groups, this research emphasizes the potential of UTE-MT MRI techniques in evaluating age-related skeletal muscle changes.

Initial findings using high-resolution magnetic resonance imaging for visualisation of the sural nerve and surrounding anatomy in healthy volunteers at 7 Tesla.

Histopathological diagnosis is the gold standard in many acquired inflammatory, infiltrative and amyloid based peripheral nerve diseases and a sensory nerve biopsy of sural or superficial peroneal nerve is favoured where a biopsy is deemed necessary. The ability to determine nerve pathology by high-resolution imaging techniques resolving anatomy and imaging characteristics might improve diagnosis and obviate the need for biopsy in some. The sural nerve is anatomically variable and occasionally adjacent vessels can be sent for analysis in error. Knowing the exact position and relationships of the nerve prior to surgery could be clinically useful and thus reliably resolving nerve position has some utility. 7T images of eight healthy volunteers' (HV) right ankle were acquired in a pilot study using a double-echo in steady-state sequence for high-resolution anatomy images. Magnetic Transfer Ratio images were acquired of the same area. Systematic scoring of the sural, tibial and deep peroneal nerve around the surgical landmark 7 cm from the lateral malleolus was performed (number of fascicles, area in voxels and mm2, diameter and location relative to nearby vessels and muscles). The sural and tibial nerves were visualised in the high-resolution double-echo in steady-state (DESS) image in all HV. The deep peroneal nerve was not always visualised at level of interest. The MTR values were tightly grouped except in the sural nerve where the nerve was not visualised in two HV. The sural nerve location was found to be variable (e.g., lateral or medial to, or crossing behind, or found positioned directly posterior to the saphenous vein). High-resolution high-field images have excellent visualisation of the sural nerve and would give surgeons prior knowledge of the position before surgery. Basic imaging characteristics of the sural nerve can be acquired, but more detailed imaging characteristics are not easily evaluable in the very small sural and further developments and specific studies are required for any diagnostic utility at 7T.

Joint k-ω Space Image Reconstruction and Data Fitting for Chemical Exchange Saturation Transfer Magnetic Resonance Imaging.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a novel MRI technology to image certain compounds at extremely low concentrations. Long acquisition time to measure signals at a set of offset frequencies of the Z-spectra and to repeat measurements to reduce noise pose significant challenges to its applications. This study explores correlations of CEST MR images along the spatial and Z-spectral dimensions to improve MR image quality and robustness of magnetization transfer ratio (MTR) asymmetry estimation via a joint k-ω reconstruction model. The model was formulated as an optimization problem with respect to MR images at all frequencies ω, while incorporating regularizations along the spatial and spectral dimensions. The solution was subject to a self-consistency condition that the Z-spectrum of each pixel follows a multi-peak data fitting model corresponding to different CEST pools. The optimization problem was solved using the alternating direction method of multipliers. The proposed joint reconstruction method was evaluated on a simulated CEST MRI phantom and semi-experimentally on choline and iopamidol phantoms with added Gaussian noise of various levels. Results demonstrated that the joint reconstruction method was more tolerable to noise and reduction in number of offset frequencies by improving signal-to-noise ratio (SNR) of the reconstructed images and reducing uncertainty in MTR asymmetry estimation. In the choline and iopamidol phantom cases with 10.5% noise in the measurement data, our method achieved an averaged SNR of 31.0 dB and 32.2 dB compared to the SNR of 24.7 dB and 24.4 dB in the conventional reconstruction approach. It reduced uncertainty of the MTR asymmetry estimation over all regions of interest by 54.4% and 43.7%, from 1.71 and 2.38 to 0.78 and 1.71, respectively.

Hippocampal Glutamate Levels and Their Correlation With Subregion Volume in School-Aged Children With MRI-Negative Epilepsy: A Preliminary Study.

Abnormal levels of glutamate constitute a key pathophysiologic mechanism in epilepsy. The use of glutamate chemical exchange saturation transfer (GluCEST) imaging to measure glutamate levels in pediatric epilepsy is rarely reported in research. To investigate hippocampal glutamate level variations in pediatric epilepsy and the correlation between glutamate and hippocampal subregional volumes. Cross-sectional, prospective. A total of 38 school-aged pediatric epilepsy patients with structurally normal MRI as determined by at least two independent radiologists (60% males; 8.7 ± 2.5 years; including 20 cases of focal pediatric epilepsy [FE] and 18 cases of generalized pediatric epilepsy [GE]) and 17 healthy controls (HC) (41% males; 9.0 ± 2.5 years). 3.0 T; 3D magnetization prepared rapid gradient echo (MPRAGE) and 2D turbo spin echo GluCEST sequences. The relative concentration of glutamate was calculated through pixel-wise magnetization transfer ratio asymmetry (MTRasym) analysis of the GluCEST data. Hippocampal subfield volumes were computed from MPRAGE data using FreeSurfer. This study used t tests, one-way analysis of variance, Kruskal-Wallis tests, and Pearson correlation analysis. P < 0.05 was considered statistically significant. The MTRasym values of both the left and right hippocampi were significantly elevated in GE (left: 2.51 ± 0.23 [GE] vs. 2.31 ± 0.12 [HCs], right: 2.50 ± 0.22 [GE] vs. 2.27 ± 0.22 [HCs]). The MTRasym values of the ipsilateral hippocampus were significantly elevated in FE (2.49 ± 0.28 [ipsilateral] vs. 2.29 ± 0.16 [HCs]). The MTRasym values of the ipsilateral hippocampus were significantly increased compared to the contralateral hippocampus in FE (2.49 ± 0.28 [ipsilateral] vs. 2.35 ± 0.34 [contralateral]). No significant differences in hippocampal volume were found between different groups (left hippocampus, P = 0.87; right hippocampus, P = 0.87). GluCEST imaging have potential for the noninvasive measurement of glutamate levels in the brains of children with epilepsy. 2 TECHNICAL EFFICACY: Stage 1.

Cerebrospinal Fluid-In Gradient of Cortical and Deep Gray Matter Damage in Multiple Sclerosis.

A CSF-in gradient in cortical and thalamic gray matter (GM) damage has been found in multiple sclerosis (MS). We concomitantly explored the patterns of cortical, thalamic, and caudate microstructural abnormalities at progressive distances from CSF using a multiparametric MRI approach. For this cross-sectional study, from 3T 3D T1-weighted scans, we sampled cortical layers at 25%-50%-75% depths from pial surface and thalamic and caudate bands at 2-3-4 voxels from the ventricular-GM interface. Using linear mixed models, we tested between-group comparisons of magnetization transfer ratio (MTR) and R2* layer-specific z-scores, CSF-in across-layer z-score changes, and their correlations with clinical (disease duration and disability) and structural (focal lesions, brain, and choroid plexus volume) MRI measures. We enrolled 52 patients with MS (33 relapsing-remitting [RRMS], 19 progressive [PMS], mean age: 46.4 years, median disease duration: 15.1 years, median: EDSS 2.0) and 70 controls (mean age 41.5 ± 12.8). Compared with controls, RRMS showed lower MTR values in the outer and middle cortical layers (false-discovery rate [FDR]-p ≤ 0.025) and lower R2* values in all 3 cortical layers (FDR-p ≤ 0.016). PMS had lower MTR values in the outer and middle cortical (FDR-p ≤ 0.016) and thalamic (FDR-p ≤ 0.048) layers, and in the outer caudate layer (FDR-p = 0.024). They showed lower R2* values in the outer cortical layer (FDR-p = 0.003) and in the outer thalamic layer (FDR-p = 0.046) and higher R2* values in all 3 caudate layers (FDR-p ≤ 0.031). Both RRMS and PMS had a gradient of damage, with lower values closer to the CSF, for cortical (FDR-p ≤ 0.002) and thalamic (FDR-p ≤ 0.042) MTR. PMS showed a gradient of damage for cortical R2* (FDR-p = 0.005), thalamic R2* (FDR-p = 0.004), and caudate MTR (FDR-p ≤ 0.013). Lower MTR and R2* of outer cortical, thalamic, and caudate layers and steeper gradient of damage toward the CSF were significantly associated with older age, higher T2-hyperintense white matter lesion volume, higher thalamic lesion volume, and lower brain volume (β ≥ 0.08, all FDR-p ≤ 0.040). Lower MTR of outer caudate layer was associated with more severe disability (β = -0.26, FDR-p = 0.040). No correlations with choroid plexus volume were found. CSF-in damage gradients are heterogeneous among different GM regions and through MS course, possibly reflecting different dynamics of demyelination and iron loss/accumulation.

QOL-23. POTENTIAL MYELIN REPAIR AFTER IRRADIATED PEDIATRIC BRAIN TUMOR: A MAGNETIZATION TRANSFER IMAGING ANALYSIS

Abstract BACKGROUND Exercise training and metformin treatment may improve cognition after cranial irradiation in pediatric brain tumors (PBT), but the neuronal mechanisms underlying the effect of these interventions remains unknown. Magnetization transfer imaging (MTI) is an imaging technique that may be sensitive to white matter microstructure – including myelin. METHODS In this work, we analyzed changes in magnetization transfer ratio (MTR) over a 12-week period in irradiated PBT survivors who participated in pilot clinical trials entailing 12 weeks of exercise training (exercise group, n=17), or metformin treatment (n=12). Pre- and post-intervention assessment included MRI scanning and neurocognitive tests. A no intervention control group, (n=7) was also included and seen before and after a 12 week period of time. We used a longitudinal Tract-Based Spatial Statistics (TBSS) approach to analyze differences in MTR across the 12 weeks in the three groups, using as covariates: age at baseline, sex, handedness, age at diagnosis and delay from diagnosis. Then we performed correlations between mean MTR changes and behavioral outcomes. RESULTS Clusters of significant increase in MTR were observed in the right temporal lobe in the exercise group after intervention and in the right minor forceps in the metformin group after treatment. These changes respectively correlated with higher performance in free recall score in exercise group and with higher performances in inhibitory control and attention in metformin group. There was no difference in MTR changes between groups nor within the control group. DISCUSSION This exploratory work suggests either a 12-week period of exercise training or metformin may promote myelination in PBT survivors in brain regions. These changes appear to be associated with improved memory and executive function, two core domains of neurocognitive deficit in this population.

Effect of reducing isoflurane level on glucosamine uptake in the mouse brain during magnetic resonance imaging studies

Anesthesia is often required during magnetic resonance imaging (MRI) examinations in animal studies. Anesthetic drugs differ in their capacity to interfere with homeostatic mechanisms responsible for glucose metabolism in the brain, which may create a constraint in the study design. Recent studies suggest that the chemical exchange saturation transfer (CEST) MRI scanning technique can detect localized metabolic changes in rodent brains induced by the uptake of glucose or its analogs; however, most of these studies do not account for the impact of anesthesia type on the brain metabolism. Herein, we aimed to evaluate the effect of reduced isoflurane levels on the preclinical imaging of glucosamine (GlcN) uptake in healthy mouse brains to establish optimal conditions for future brain imaging studies using the CEST MRI technique. The commonly used anesthesia protocol for longitudinal MRI examinations using 1.5% isoflurane level was compared to that using a mixture of low isoflurane (0.8%) level combined with midazolam (2 mg/kg, SC). Magnetization transfer ratio asymmetry (MTRasym) and area under the curve (AUC) analyses were used to characterize GlcN signals in the brain. The results indicated that mice injected with GlcN and anesthetized with 1.5% isoflurane exhibited low and insignificant changes in the MTRasym and AUC signals in the frontal cortex, whereas mice administered with 0.8% isoflurane combined with midazolam demonstrated a significant increase in these signals in the frontal cortex. This study highlights the diverse GlcN metabolic changes observed in mouse brains under variable levels of isoflurane anesthesia using the CEST MRI method. The results suggest that it is feasible to maintain anesthesia with low-dose isoflurane by integrating midazolam, which may enable the investigation of GlcN uptake in the brain. Thus, reducing isoflurane levels may support studies into mouse brain metabolism using the CEST MRI method and should be considered in future studies.

Preliminary exploration of amide proton transfer weighted imaging in differentiation between benign and malignant bone tumors.

To explore the value of 3D amide proton transfer weighted imaging (APTWI) in the differential diagnosis between benign and malignant bone tumors, and to compare the diagnostic performance of APTWI with traditional diffusion-weighted imaging (DWI). Patients with bone tumors located in the pelvis or lower limbs confirmed by puncture or surgical pathology were collected from January 2021 to July 2023 in the First Affiliated Hospital of Zhengzhou University. All patients underwent APTWI and DWI examinations. The magnetization transfer ratio with asymmetric analysis at the frequency offset of 3.5 ppm [MTRasym(3.5 ppm)] derived by APTWI and the apparent diffusion coefficient (ADC) derived by DWI for the tumors were measured. The Kolmogorou-Smirnou and Levene normality test was used to confirm the normal distribution of imaging parameters; and the independent sample t test was used to compare the differences in MTRasym(3.5 ppm) and ADC between benign and malignant bone tumors. In addition, the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of different imaging parameters in differentiation between benign and malignant bone tumors. P<0.05 means statistically significant. Among 85 bone tumor patients, 33 were benign and 52 were malignant. The MTRasym(3.5 ppm) values of malignant bone tumors were significantly higher than those of benign tumors, while the ADC values were significantly lower in benign tumors. ROC analysis shows that MTRasym(3.5 ppm) and ADC values perform well in the differential diagnosis of benign and malignant bone tumors, with the area under the ROC curve (AUC) of 0.798 and 0.780, respectively. Combination of MTRasym(3.5 ppm) and ADC values can further improve the diagnostic performance with the AUC of 0.849 (sensitivity = 84.9% and specificity = 73.1%). MTRasym(3.5 ppm) of malignant bone tumors was significantly higher than that of benign bone tumors, reflecting the abnormal increase of protein synthesis in malignant tumors. APTWI combined with DWI can achieve a high diagnostic efficacy in differentiation between benign and malignant bone tumors.

One-Year Longitudinal Assessment of Patients With CMT1A Using Quantitative MRI.

Intramuscular fat fraction (FF) assessed using quantitative MRI (qMRI) has emerged as one of the few responsive outcome measures in CMT1A suitable for future clinical trials. This study aimed to identify the relevance of multiple qMRI biomarkers for tracking longitudinal changes in CMT1A and to assess correlations between MRI metrics and clinical parameters. qMRI was performed in CMT1A patients at 2 time points, a year apart, and various metrics were extracted from 3-dimensional volumes of interest at thigh and leg levels. A semiautomated segmentation technique was used, enabling the analysis of central slices and a larger 3D muscle volume. Metrics included proton density (PD), magnetization transfer ratio (MTR), and intramuscular FF. The sciatic and tibial nerves were also assessed. Disease severity was gauged using Charcot Marie Tooth Neurologic Score (CMTNSv2), Charcot Marie Tooth Examination Score, Overall Neuropathy Limitation Scale scores, and Medical Research Council (MRC) muscle strength. Twenty-four patients were included. FF significantly rose in the 3D volume at both thigh (+1.04% ± 2.19%, p = 0.041) and leg (+1.36% ± 1.87%, p = 0.045) levels. The 3D analyses unveiled a length-dependent gradient in FF, ranging from 22.61% ± 10.17% to 26.17% ± 10.79% at the leg level. There was noticeable variance in longitudinal changes between muscles: +3.17% ± 6.86% (p = 0.028) in the tibialis anterior compared with 0.37% ± 4.97% (p = 0.893) in the gastrocnemius medialis. MTR across the entire thigh volume showed a significant decline between the 2 time points -2.75 ± 6.58 (p = 0.049), whereas no significant differences were noted for the 3D muscle volume and PD. No longitudinal changes were observed in any nerve metric. Potent correlations were identified between FF and primary clinical measures: CMTNSv2 (ρ = 0.656; p = 0.001) and MRC in the lower limbs (ρ = -0.877; p < 0.001). Our results further support that qMRI is a promising tool for following up longitudinal changes in CMT1A patients, FF being the paramount MRI metric for both thigh and leg regions. It is crucial to scrutinize the postimaging data extraction methods considering that annual changes are minimal (around +1.5%). Given the varied FF distribution, the existence of a length-dependent gradient, and the differential fatty involution across muscles, 3D volume analysis appeared more suitable than single slice analysis.