Diffusion Magnetic Resonance Imaging Research Articles

NIMG-36. PERFUSION, DIFFUSION, AND ANATOMICAL MRI BIOMARKERS FOR ASSESSING HISTOLOGICALLY-CONFIRMED MALIGNANT TRANSFORMATION IN MOLECULAR SUBTYPES OF IDH-MUTANT GLIOMAS

Abstract BACKGROUND Isocitrate dehydrogenase-mutant (IDHm) gliomas often initially present as low-grade (grade 2) gliomas but are expected to later progress into more aggressive higher-grade (grade 3-4) gliomas through malignant transformation (MT). MT is often determined non-invasively by emergence of contrast-enhancement on post-contrast T1-weighted magnetic resonance imaging (MRI), but contrast-enhancement is an imperfect surrogate for histologically-confirmed MT. This study explored perfusion, diffusion, and anatomical MRI biomarkers besides contrast-enhancement to study histologically-confirmed MT in IDHm 1p/19q-intact astrocytomas (IDHm-A) and IDHm 1p/19q-co-deleted oligodendrogliomas (IDHm-O). METHODS N=64 patients with initial histopathological grade 2 IDH-mutant glioma diagnosis who underwent repeated tissue sampling and were classified as histologically-confirmed MT (n=35) or non-MT (n=29) were retrospectively studied. Pre-surgical anatomical MRI (n=64) and, if available, diffusion-weighted imaging (n=61) and dynamic susceptibility contrast perfusion MRI (n=53) were analyzed. Tumor volumes of interest were segmented on the whole T2/FLAIR-hyperintense tumor. Measurable contrast enhancement (>1000mm3), tumor volume, sphericity, median apparent diffusion coefficient (ADC), and normalized relative cerebral blood volume (nrCBV) were compared between MT vs. non-MT IDHm-A and IDHm-O. RESULTS 81% of contrast-enhancing IDHm-A and 100% of contrast-enhancing IDHm-O underwent MT, while 41% of MT IDHm-A and 62% of MT IDHm-O were non-enhancing. Tumor volumes were significantly larger in the MT vs. non-MT groups for both IDHm-A (P=0.02) and IDHm-O (P=0.04). Whole tumor nrCBV was significantly higher (P=0.002), whole tumor ADC trended lower (P=0.06), and non-enhancing tumor sphericity was significantly lower (P=0.03) in MT vs. non-MT IDHm-A. There were no significant differences in ADC, nrCBV, nor sphericity when comparing MT vs. non-MT IDHm-O (P>0.05). CONCLUSIONS Many MT IDHm-gliomas remain non-enhancing. Tumor volumes can determine MT for both IDHm-A and IDHm-O. Diffusion and perfusion MRI show differences for MT in IDHm-A but not IDHm-O, which may reflect the different tumor biology of these IDHm molecular subtypes and their need for separate imaging biomarkers.

Investigation of the Relationship of Sleep Disorder Occurring in Fibromyalgia with Central Nervous System and Pineal Gland Volume.

Mechanisms of sleep disorders in fibromyalgia (FM) patients, such as insomnia, early morning awakenings and poor quality sleep, have not yet been proven and no consistent and effective treatment is yet available. The aim of this study was to investigate the pineal gland volume and the relationship between total fiber count, total fiber volume and total fiber length of the spinoreticular tract involved in regulation of sleep and wakefulness in terms of the mechanism of sleep disturbance. This study included only female cases, 31 with fibromyalgia and 31 controls. Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Tractography of targeted pathway from brain diffusion MR images was calculated in DSI Studio program and the volume of the pineal gland was calculated in ITK-SNAP program. The mean volume of the pineal gland was higher in control group (218.84±64.45 mm3) than in fibromyalgia group (174.77±48.65 mm3), which was statistically significant (p=0.004). However, there was no statistically significant difference between two groups in total spinoreticular tract (TSRT), total volume (TSRTV), TSRT FA, TSRT MD, TSRT AD and TSRT RD of spinoreticular tract, which is involved in the regulation of sleep and wakefulness (p>0.05). In conclusion, it is thought that the endocrine system may be more related to sleep disturbance in individuals with FM than central nervous system. Therefore, we believe that it may be more appropriate to work on the endocrine system rather than neural system in the treatment of sleep disturbance in patients with FM.

NIMG-29. EARLY REDUCTION IN MRI DIFFUSION APPARENT DIFFUSION COEFFICIENT (ADC) STRONGLY PREDICTS LONG TERM RESPONSE TO ONC201 THERAPY IN PATIENTS WITH H3K27M-DMG

Abstract ONC201 is the first monotherapy to improve outcomes in H3K27M- diffuse midline glioma (DMG) beyond radiation. Despite impressive early efficacy in H3K27M-DMG, individual response to ONC201 is variable and no radiographic biomarkers predict long term response. Previous studies demonstrated baseline MRI diffusion apparent diffusion coefficient (ADC) is lower in DMG with H3K27M compared to wildtype but change after radiation therapy was not correlated with improved OS or PFS. We hypothesize ADC will enable stratification of patients more likely to respond to ONC201. Imaging and clinical data were abstracted from chart review of patients treated with ONC201 at University of Michigan. Two neuroradiologists performed centralized review for RAPNO measurements and mean ADC was assessed using ROI measured in consistent anatomic locations, with areas of cystic degeneration or necrosis excluded. Sixty-one patients were identified for review. Preliminary analysis was performed on twenty-three patients, with upfront ONC201 therapy, median age 14.8 years old (5-25yo), primary site includes pontine (n=15), thalamic (n=7). Baseline characteristics of age, ADC and size at diagnosis or follow-up RAPNO scored size were not statistically significant. Patients with longer than median survival (334 days) demonstrated increased ADC (+58.25x10-6mm2/s) from baseline to cycle 2 whereas patients with shorter than median survival demonstrated decreased ADC (-174.8x10-6mm2/s) (p = 0.0076). Further, patients with decreased ADC demonstrated mean OS of 302.8 days and patients with increased ADC had mean OS of 588.0 (p = 0.0054). In H3K27M-DMG patients treated with ONC201, increased ADC after two cycles of ONC201 was strongly predictive of longer overall survival. Our recent work demonstrated that ONC201 disrupts metabolic and epigenetic pathways to restore pathognomonic H3K27me3 reduction, which may underline greater change in ADC. Ongoing work will validate these findings in an independent external cohort and integrate histogram analysis, parametric assessments, MRI perfusion and liquid biopsy biomarkers (cf-tDNA and metabolomics).

Diagnostic Utility of Diffusion-Weighted Imaging in Distinguishing Common Pediatric Posterior Fossa Tumors: A Single Center Retrospective Study.

Pediatric posterior fossa tumors pose diagnostic challenges due to their diverse histopathological features and variable clinical presentations. Conventional magnetic resonance imaging (MRI) serves as the initial diagnostic tool; however, additional modalities, such as diffusion-weighted imaging (DWI), are essential for refining tumor classification. This retrospective single-center study aimed to evaluate the diagnostic utility of apparent diffusion coefficient (ADC) parameters in distinguishing between the most common pediatric posterior fossa tumors. Fifty-nine patients under the age of 18 (27 females and 32 males) with histopathologically diagnosed primary posterior fossa tumors underwent pre-treatment conventional and diffusion MRI. Apparent diffusion coefficient values were measured from solid tumor regions and normal cerebellar parenchyma, with subsequent calculation of tumor/normal cerebellar ADC ratios. The median ADC values for pilocytic astrocytomas (PAs) were 1786.2 × 10-6 mm2 /s, ependymomas 1144.9 × 10-6 mm2 /s, and for medulloblastomas 666.1 × 10-6 mm2 /s were significantly different (P < .001 for all three). Similarly, the median ADC ratios demonstrated discriminatory potential, with PAs showing the highest ratio (2.46), followed by ependymomas (1.55) and medulloblastomas (0.89) (P < .001 for all three). Receiver operating characteristic analysis revealed distinct ADC cutoffs and ratios for differentiating all tumor types from each other. Despite limitations, such as a small cohort size and different MRI protocols, our results show that ADC metrics are especially useful for distinguishing between the most common pediatric posterior fossa tumors. We recommend that future studies integrate advanced imaging techniques and larger cohorts to improve diagnostic accuracy.

Are background breast parenchymal features on preoperative breast MRI associated with disease-free survival in patients with invasive breast cancer?

To evaluate whether breast parenchymal features of the contralateral breast on preoperative MRI are associated with primary breast cancer characteristics and disease-free survival (DFS) in women with invasive breast cancer. Women with newly diagnosed invasive breast cancer who underwent preoperative breast MRI followed by surgery were retrospectively evaluated. Background parenchymal enhancement (BPE) on dynamic contrast-enhanced MRI and background diffusion signal (BDS) on diffusion-weighted MRI of the contralateral breast were qualitatively assessed using a four-category scale: minimal, mild, moderate, or marked. Primary breast cancer characteristics were compared based on the degree of BPE or BDS. Cox proportional hazards models were used to evaluate the association between MRI parenchymal features and DFS after adjusting for clinicopathologic features. A total of 515 women (mean age, 54years) were included. Of whom, 46 (8.9%) patients who developed disease recurrence at a median follow-up of 60months were observed. A high level (moderate/marked) of BPE or BDS was associated with younger age (≤ 45) and premenopausal status (all P < 0.05) compared to a low level (minimal/mild), but it was not associated with primary cancer characteristics such as tumor stage, grade, or subtype. Multivariable Cox proportional hazards analysis demonstrated that larger tumor size (> 2cm) (hazard ratio [HR], 3.877; P < . 001), triple-negative subtype (HR, 2.440; P = .013), and axillary node metastasis (HR, 1.823; P = .049) were associated with worse DFS. No associations were observed between background parenchymal features and disease outcomes. MRI parenchymal features, including BPE and BDS, of the contralateral breast showed no associations with primary breast cancer characteristics or DFS in women with invasive breast cancer.

Deep learning‐based reconstruction on intensity‐inhomogeneous diffusion magnetic resonance imaging

Deep learning‐based reconstruction on intensity‐inhomogeneous diffusion magnetic resonance imaging

Evaluation of Glymphatic System Development in Neonatal Brain via Diffusion Analysis along the Perivascular Space Index.

Glymphatic system is a recently discovered macroscopic waste clearance system associated with numerous neurological diseases. However, little is known about glymphatic system development in neonates. We sought to evaluate diffusion along the perivascular space (ALPS) index, a proxy for glymphatic system function, in neonates and investigate its potential associations with maturation, sex, and preterm birth. Diffusion magnetic resonance imaging (MRI) data in 418 neonates, including 92 preterm neonates (57 males) and 326 term neonates (175 males), from the Developing Human Connectome Project were used for evaluating ALPS index. Linear regression modeling was performed to assess group differences in the ALPS index according to preterm birth and sex. Pearson's and partial correlation analysis were performed to assess the association between the ALPS index and gestational age (GA) as well as postmenstrual age (PMA) at MRI. Moderation analysis was performed to assess the moderation effect of preterm birth on the relationship between the ALPS index and PMA. Compared to term neonates, preterm neonates exhibited lower ALPS indices (p < 0.001). The ALPS index positively correlated with PMA (p = 0.004) and GA (p < 0.001). Preterm birth (p = 0.013) had a significant moderation effect on the relationship between the ALPS index and PMA. Sex had no significant direct effect (p = 0.639) or moderation effect (p = 0.333) on ALPS index. Glymphatic system development is a dynamic process in neonates, which can be moderated by preterm birth, the ALPS index could serve as a sensitive biomarker for monitoring this process. ANN NEUROL 2024;96:970-980.

Rebalance the Inhibitory System in the Elderly Brain: Influence of Balance Learning on GABAergic Inhibition and Functional Connectivity.

Aging involves complex processes that impact the structure, function, and metabolism of the human brain. Declines in both structural and functional integrity along with reduced local inhibitory tone in the motor areas, as indicated by reduced γ-aminobutyric acid (GABA) levels, are often associated with compromised motor performance in elderly adults. Using multimodal neuroimaging techniques including magnetic resonance spectroscopy (MRS), diffusion magnetic resonance imaging (MRI), functional MRI as well as transcranial magnetic stimulation to assess short-interval intracortical inhibition (SICI), this study explores whether these age-related changes can be mitigated by motor learning. The investigation focused on the effects of long-term balance learning (3 months) on intracortical inhibition, metabolism, structural, and functional connectivity in the cortical sensorimotor network among an elderly cohort. We found that after 3 months of balance learning, subjects significantly improved balance performance, upregulated sensorimotor cortical GABA levels and ventral sensorimotor network functional connectivity (VSN-FC) compared to a passive control group. Furthermore, correlation analysis suggested a positive association between baseline VSN-FC and balance performance, between baseline VSN-FC and SICI, and between improvements in balance performance and upregulation in SICI in the training group, though these correlations did not survive the false discovery rate correction. These findings demonstrate that balance learning has the potential to counteract aging-related decline in functional connectivity and cortical inhibition on the "tonic" (MRS) and "functional" (SICI) level and shed new light on the close interplay between the GABAergic system, functional connectivity, and behavior.

Dissociation of White Matter Bundles in Different Recovery Measures in Poststroke Aphasia.

Poststroke aphasia (PSA) recovery shows high variability across individuals and at different time points. Although diffusion biomarkers from the ventral and dorsal streams have demonstrated strong predictive power for language outcomes, it is still unclear how these biomarkers relate to the various stages of PSA recovery. In this study, we aim to compare diffusion metrics and language measures as predictors of language recovery in a longitudinal cohort of participants with PSA. Participants were recruited at a stroke unit at the emergency room, and underwent diffusion magnetic resonance imaging scanning and language assessment within 3 days (acute phase) after stroke, with behavioral follow-ups at subacute (10±3 days) and chronic phases (>6 months). We conducted regression analyses on language performance (cross-sectional), Δscores between all time points (acute-subacute, subacute-chronic, acute-chronic), and relative Δscores between all time points (Δscore/language baseline score), with acute diffusion metrics from language-related white matter tracts, lesion size, language baseline scores, and demographic data as predictors. Thirty-nine participants presenting PSA were recruited, and 24 participants (mean age, 73 years; 8 women) completed the 3-time point assessment in total. The best prediction model of performance scores used axial diffusivity from the left arcuate fasciculus in both the subacute (R2=0.785) and chronic stages (R2=0.626). Moreover, the prediction of ∆scores depended on axial diffusivity from the left inferior frontal-occipital fasciculus in the subacute stage (R2=0.5) and depended additionally on axial diffusivity from the right inferior frontal-occipital fasciculus in the chronic stage (R2=0.68). The prediction of mediation analyses showed that the lesion load of the left arcuate fasciculus mediated the relationship between axial diffusivity from the left arcuate fasciculus and chronic language performance. Language performance at subacute and chronic time points could be predicted by the integrity of the left arcuate fasciculus, whereas Δscores in the subacute and chronic phases depended on the left inferior frontal-occipital fasciculus, showing a dissociation of the white matter pathways about language outcomes. These results suggest a functional differentiation of the dual-stream components in PSA recovery.

Radiofrequency Enhancer to Recover Signal Dropouts in 7 Tesla Diffusion MRI.

Diffusion magnetic resonance imaging (dMRI) allows for a non-invasive visualization and quantitative assessment of white matter architecture in the brain by characterizing restrictions on the random motion of water molecules. Ultra-high field MRI scanners, such as those operating at 7 Tesla (7T) or higher, can boost the signal-to-noise ratio (SNR) to improve dMRI compared with what is attainable at conventional field strengths such as 3T or 1.5T. However, wavelength effects at 7T cause reduced transmit magnetic field efficiency in the human brain, mainly in the posterior fossa, manifesting as signal dropouts in this region. Recently, we reported a simple approach of using a wireless radiofrequency (RF) surface array to improve transmit efficiency and signal sensitivity at 7T. In this study, we demonstrate the feasibility and effectiveness of the RF enhancer in improving in vivo dMRI at 7T. The electromagnetic simulation results demonstrated a 2.1-fold increase in transmit efficiency with the use of the RF enhancer. The experimental results similarly showed a 1.9-fold improvement in transmit efficiency and a 1.4-fold increase in normalized SNR. These improvements effectively mitigated signal dropouts in regions with inherently lower SNR, such as the cerebellum, resulting in a better depiction of principal fiber orientations and an enhanced visualization of extended tracts.

Goal-Oriented Attentional Self-Regulation Training in Chronic Mild Traumatic Brain Injury is Linked to Microstructural Plasticity in Prefrontal White Matter.

Impaired attention is one of the most common, debilitating, and persistent consequences of traumatic brain injury (TBI), which impacts overall cognitive and executive functions in these patients. Previous neuroimaging studies, trying to understand the neural mechanism underlying attention impairment post TBI, have highlighted the role of prefrontal white matter tracts in attentional functioning in mild TBI (mTBI). Goal-Oriented Attentional Self-Regulation (GOALS) is a cognitive rehabilitation training program that targets executive control functions in participants by applying mindfulness-based attention regulation and goal management strategies. GOALS training has been demonstrated to improve attention and executive functioning in patients with chronic TBI. However, its impact on microstructural integrity of attention-associated prefrontal white matter tracts is still unclear. Here, using diffusion magnetic resonance imaging in a pilot randomized controlled trial, we investigated the effect of GOALS training on prefrontal white matter microstructure in 19 U.S. military veterans with chronic mTBI, compared with a matched control group of 14 veterans with chronic mTBI who received standard of care brain health education. We also tested for an association between microstructural white matter changes and sustained attention ability in these patients pre- and post-GOALS training. Our results show significantly better white matter microstructural integrity in left and right anterior corona radiata (ACR) in the GOALS group compared with the control group post-training. Moreover, we found a significant correlation between sustained attention ability of GOALS training participants and white matter integrity of their right ACR pre- and post-training. Finally, our findings indicated that the improved white matter integrity of the ACR in GOALS training participants was the result of increased neurite density and decreased fiber orientation dispersion within this tract.

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.

Ex vivo magnetic resonance imaging of the human fetal brain.

The fetal brain undergoes a dynamic process of development during gestation, marked by well-orchestrated events such as neuronal proliferation, migration, axonal outgrowth, and dendritic arborization, mainly elucidated through histological studies. Ex vivo magnetic resonance imaging (MRI) has emerged as a useful tool for 3D visualization of the developing fetal brain, serving as a complementary tool to traditional histology. In this review, we summarized the commonly employed ex vivo MRI techniques and their advances in fetal brain imaging, as well as a standard protocol for postmortem fetal brain specimen collection and fixation. We then provided an overview of ex vivo MRI-based studies on the fetal brain. According to our review, ex vivo T1- or T2-weighted structural MRI has contributed to the characterization of the anatomy of transient neuronal proliferative zones, the basal ganglia, and the cortex. Diffusion MRI related techniques, such as diffusion tensor imaging and tractography, have helped to investigate the microstructural patterns of fetal brain tissue, as well as the early emergence and development of neuronal migration pathways and white matter bundles. Ex vivo MRI findings have shown strong histological correlations, supporting the potential of MRI in evaluating the developmental events in the fetal brain. Postmortem MRI examinations have also demonstrated comparable, and in certain cases, superior performance to traditional autopsy in revealing fetal brain abnormalities. In conclusion, ex vivo fetal brain MRI is an invaluable tool that provides unique insights into the early stages of brain development.

Infantile Intraparenchymal Brain Abscess due to Streptococcus pyogenes

Introduction Group A ß-hemolytic streptococcus (GABHS) are the most common bacterial cause of tonsillitis, and can cause noninvasive diseases such as pharyngitis and impetigo, as well as more severe invasive diseases. The incidence of invasive disease is 1-3/100,000 per year, and the morbidity and mortality rate is high. GABHS is rarely lead to brain abscesses. Case Report Acute phase reactants were found to be high in a 40-day-old patient who presented with fever, irritability and focal seizures. Acute phase reactants were high. Transfontanel ultrasonography showed increased thickness, echo and blood supply in the meninges. Brain magnetic resonance imaging (MRI) and diffusion MRI revealed a thick-walled abscess in the right cerebral hemisphere and parietooccipital parenchyma with diffusion restriction on diffusion-weighted images. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) test revealed S. pyogenes,and S. pyogenes grown in CSF culture. Initially, meropenem, vancomycin, metronidazole antibiotherapy was applied. Treatment was revised to cefotaxime and vancomycin after culture antibiogram and was completed for 8 weeks. Seizures regressed. Control brain imaging showed improvement. Restriction in left lower extremity movements remained. Physical therapy and rehabilitation was recommended and he was discharged. Conclusion GABHS, which is the causative agent of acute tonsillitis, rarely causes invasive disease which has high mortality and morbidity.

Magnetic resonance imaging quantitative assessment of corticospinal tract damage in basal ganglia infarction.

To retrospectively explore the role of magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) in analyzing the corticospinal tract injury in acute cerebral anterior circulation infarction in the basal ganglia region and the correlation between DTI parameters and neurological function scores, patients with acute cerebral infarction and stroke had undergone plain MRI and DTI sequence scanning were enrolled. Diffusion tensor tractography was used to perform 3-dimensional reconstruction of bilateral corticospinal tracts (CST). The image data were processed to obtain fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values, and the correlation between the DTI parameters and neurological function scores of National Institutes of Health Stroke Scale (NIHSS) was evaluated. A total of thirty-two patients with acute ischemic cerebral infarction were retrospectively enrolled, including 19 males and 13 females with a mean age 63.22 ± 7.78 years. The CST score was 0 in 2 (6.25%) patients, 1 in 9 (28.13%), 2 in 9 (28.13%), 3 in 7 (21.88%), and 4 in 5 (15.63%). The FA value significantly (P = .01) decreased (0.52 ± 0.03 vs 0.62 ± 0.04) on the ischemic side compared with that on the normal side. A significant (P < .05) difference was detected in the number of nerve fibers (223.3 ± 110.0 vs 246.7 ± 104.4) rather than in the ADC values (0.86 ± 0.06 vs 0.84 ± 0.06) between the ischemic and healthy sides. The FA and ADC values were not significantly (P > .05) different according to the CST scores 0, 1, 2, 3, or 4 between the ischemic and healthy sides. There was a significant (P < .05) negative correlation between the FA value on the infarcted side and the NIHSS score. In conclusion, with the DTI technology, varying degrees of damage to the corticospinal tract at the infarcted side can be detected and important clinical information can be provided for the diagnosis and prognosis of acute cerebral infarction by evaluating the degree of corticospinal tract injury.

Hippocampal microscopic fractional anisotropy is reduced in temporal lobe epilepsy

Abstract Surgical resection is the method of choice for treating drug-resistant focal temporal lobe epilepsy (TLE). Postsurgical outcomes are better when magnetic resonance imaging (MRI) findings can localize the seizure focus for resection. However, many patients are MR-negative, meaning the focus cannot be differentiated from normal tissue in relaxation-weighted MRI. Diffusion MRI shows promise as a preoperative marker of neuronal abnormalities due to its sensitivity to cellular changes such as axon damage, indexed by fractional anisotropy. Microscopic fractional anisotropy is a recently introduced diffusion MRI metric that is sensitive to axon integrity regardless of axon orientation in both grey and white matter. In contrast, regular fractional anisotropy is only sensitive to axon integrity in coherently oriented bundles of fibers. This work investigated whether microscopic fractional anisotropy is sensitive to hippocampal abnormalities in drug-resistant TLE. Diffusion MRI was performed on a 3T scanner in 19 patients (age = 31±10 years) with drug-resistant TLE (of which 10 were MR-negative) and 18 healthy volunteers (age = 38±15). A deep-learning method was employed to segment the hippocampus into smaller subregions corresponding to the subiculum, cornu ammonis (CA) 1, CA2/3, and CA4 plus dentate gyrus (DG). Mean measurements of subregion volume, diffusivity, fractional anisotropy, and microscopic fractional anisotropy were compared between cohorts. In a subset of the TLE cohort suspected to have unilateral pathology (n=15, age = 32±10 years), the percentage differences between measurements ipsilateral and contralateral to the epileptogenic zone were evaluated to assess asymmetry. Microscopic fractional anisotropy was reduced in the hippocampus of drug-resistant TLE patients relative to healthy volunteers. In subregion-specific analysis, microscopic fractional anisotropy was significantly reduced in only the CA4/DG region in patients compared to healthy volunteers, after corrections for multiple comparisons. In the 15 patients with suspected unilateral pathology, microscopic fractional anisotropy was reliably and statistically lower in the ipsilateral CA4/DG region compared to the contralateral side. Significant differences were not observed between TLE patients and healthy volunteers, or between hemispheres for patients with suspected unilateral pathology, for the fractional anisotropy or volume metrics. Diffusion MRI may complement standard imaging procedures by detecting abnormalities in MRI-negative patients. Due to its ability to detect abnormality regardless of axon orientation, microscopic fractional anisotropy may improve seizure focus localization in surgical candidates.

Single-shot echo planar time-resolved imaging for multi-echo functional MRI and distortion-free diffusion imaging.

To develop a single-shot SNR-efficient distortion-free multi-echo imaging technique for dynamic imaging applications. Echo planar time-resolved imaging (EPTI) was first introduced as a multi-shot technique for distortion-free multi-echo imaging. This work aims to develop single-shot EPTI (ss-EPTI) to achieve improved robustness to motion/physiological noise, increased temporal resolution, and higher SNR efficiency. A new spatiotemporal encoding that enables reduced phase-encoding blips and minimized echo spacing under the single-shot regime was developed, which improves sampling efficiency and enhances spatiotemporal correlation in the k-TE space for improved reconstruction. A continuous readout with minimized deadtime was employed to optimize SNR efficiency. Moreover, k-TE partial Fourier and simultaneous multi-slice acquisition were integrated for further acceleration. ss-EPTI provided distortion-free imaging with densely sampled multi-echo images at standard resolutions (e.g., ˜1.25 to 3 mm) in a single-shot. Improved SNR efficiency was observed in ss-EPTI due to improved motion/physiological-noise robustness and efficient continuous readout. Its ability to eliminate dynamic distortions-geometric changes across dynamics due to field changes induced by physiological variations or eddy currents-further improved the data's temporal stability. For multi-echo fMRI, ss-EPTI's multi-echo images recovered signal dropout in short- regions and provided TE-dependent functional information to distinguish non-BOLD noise for further tSNR improvement. For diffusion MRI, it achieved shortened TEs for improved SNR and provided images free from both B0-induced and diffusion-encoding-dependent eddy-current-induced distortions with multi-TE diffusion metrics. ss-EPTI provides SNR-efficient distortion-free multi-echo imaging with comparable temporal resolutions to ss-EPI, offering a new acquisition tool for dynamic imaging.

Quantifying the Fascicular Changes in Recovered Achilles Tendon Patients Using Diffusion Magnetic Resonance Imaging and Tractography.

Regardless of the way of treatment, persistent deficits in calf muscles in recovered patients from Achilles tendon rupture (ATR) exist long-term postinjury. Studies on calf muscle changes mostly highlight morphological changes in the calf muscles and Achilles tendon. However, limited attention has been given to fascicular changes. Diffusion tensor imaging (DTI) can provide a better understanding of the characteristics and properties of tissues with organized microstructure. In the current study, we used DTI-derived indices (mean diffusivity (MD), fractional anisotropy (FA), and eigenvalues-λ 1, λ 2, and λ 3) and fiber tractography to better understand the soleus muscle after recovery from ATR by comparing the results of injured legs with healthy ones. Our findings suggest that the standard deviations of measured parameters (FA, MD, and eigenvalues) within the soleus muscle are better predictors of the changes associated with the ATR as compared to the control counterpart for the volumetric region of interest (ROI). Additionally, in four out of five participants, smaller tracts were observed in the injured leg compared to the healthy one, as evidenced by the fiber length distribution of the tracts. Altogether, this study demonstrates the feasibility of the DTI and fiber tractography approaches to quantify the fascicular changes in the individuals recovered from ATR.

MFCA-MICNN: a convolutional neural network with multiscale fast channel attention and multibranch irregular convolution for noise removal in dMRI

Diffusion magnetic resonance imaging (dMRI) currently stands as the foremost noninvasive method for quantifying brain tissue microstructure and reconstructing white matter fiber pathways. However, the inherent free diffusion motion of water molecules in dMRI results in signal decay, diminishing the signal-to-noise ratio (SNR) and adversely affecting the accuracy and precision of microstructural data. In response to this challenge, we propose a novel method known as the Multiscale Fast Attention-Multibranch Irregular Convolutional Neural Network for dMRI image denoising. In this work, we introduce Multiscale Fast Channel Attention, a novel approach for efficient multiscale feature extraction with attention weight computation across feature channels. This enhances the model's capability to capture complex features and improves overall performance. Furthermore, we propose a multi-branch irregular convolutional architecture that effectively disrupts spatial noise correlation and captures noise features, thereby further enhancing the denoising performance of the model. Lastly, we design a novel loss function, which ensures excellent performance in both edge and flat regions. Experimental results demonstrate that the proposed method outperforms other state-of-the-art deep learning denoising methods in both quantitative and qualitative aspects for dMRI image denoising with fewer parameters and faster operational speed.

APOE 𝜀4-related blood-brain barrier breakdown is associated with microstructural abnormalities.

Blood-brain barrier (BBB) dysfunction occurs in Alzheimer's disease (AD). Yet, the stage at which it appears along the AD time course and whether it contributes to neurodegeneration remain unclear. Older adults (61 to 90 years) from cognitively normal (CN) to mildly cognitively impaired (CI), enriched for APOE 𝜀4 and amyloid positivity, underwent dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and diffusion MRI to measure BBB permeability and brain microstructure. Analysis of variance compared BBB permeability according to cognitive status, amyloid beta (Aβ), and APOE4. Linear regressions assessed associations of BBB permeability with brain microstructure and interactions with Aβ and APOE4. BBB permeability was elevated for APOE4 carriers across the cortical gray matter, with the strongest differences among CN amyloid-negative individuals. Associations between entorhinal BBB permeability and microstructure interacted with Aβ and APOE4, with the strongest relationships in amyloid-positive individuals and APOE4 carriers. APOE4 may drive widespread BBB dysfunction in preclinical AD, which may contribute to neurodegenerative changes early along the AD cascade. Gray matter blood-brain barrier (BBB) permeability is elevated for APOE4 carriers. APOE4-related BBB breakdown appears in the absence of cognitive decline or amyloid. BBB leakage correlates with entorhinal cortex microstructural injury. Associations with microstructure are strongest for amyloid-positive APOE4 carriers.