Multishell diffusion MRI reveals whole-brain white matter changes in HIV.

Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) have been previously used to explore white matter related to human immunodeficiency virus (HIV) infection. While DTI and DKI suffer from low specificity, the Combined Hindered and Restricted Model of Diffusion (CHARMED) provides additional microstructural specificity. We used these three models to evaluate microstructural differences between 35 HIV-positive patients without neurological impairment and 20 healthy controls who underwent diffusion-weighted imaging using three b-values. While significant group effects were found in all diffusion metrics, CHARMED and DKI analyses uncovered wider involvement (80% vs. 20%) of all white matter tracts in HIV infection compared with DTI. In restricted fraction (FR) analysis, we found significant differences in the left corticospinal tract, middle cerebellar peduncle, right inferior cerebellar peduncle, right corticospinal tract, splenium of the corpus callosum, left superior cerebellar peduncle, left superior cerebellar peduncle, pontine crossing tract, left posterior limb of the internal capsule, and left/right medial lemniscus. These are involved in language, motor, equilibrium, behavior, and proprioception, supporting the functional integration that is frequently impaired in HIV-positivity. Additionally, we employed a machine learning algorithm (XGBoost) to discriminate HIV-positive patients from healthy controls using DTI and CHARMED metrics on an ROIwise basis, and unique contributions to this discrimination were examined using Shapley Explanation values. The CHARMED and DKI estimates produced the best performance. Our results suggest that biophysical multishell imaging, combining additional sensitivity and built-in specificity, provides further information about the brain microstructural changes in multimodal areas involved in attentive, emotional and memory networks often impaired in HIV patients.

Sex hormones differentially contribute to Parkinson disease in males: A multimodal biomarker study.

BACKGROUND AND PURPOSE: Parkinson disease (PD) presents relevant sex-related differences in epidemiology, pathophysiology, and clinical features, with males being more vulnerable to the disease. Sex hormones might have a role, as the experimental models suggest; however, human-based evidence is scarce. Here, we integrated multimodal biomarkers to investigate the relationships between circulating sex hormones and clinical-pathological features in male PD patients. METHODS: A cohort of 63 male PD patients underwent comprehensive clinical evaluation of motor and nonmotor disturbances; measurement of estradiol, testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) blood levels; and cerebrospinal fluid (CSF) assay of total α-synuclein, amyloid-ß-42, amyloid-ß-40, total tau, and phosphorylated-181 tau levels. A subgroup of 47 PD patients underwent brain volumetry by 3-T magnetic resonance imaging for further correlations. A control group of 56 age-matched individuals was enrolled for comparative analyses. RESULTS: Male PD patients had higher estradiol and testosterone levels than controls. Estradiol had independent inverse associations with Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part 3 score and disease duration; it was also lower in nonfluctuating patients. Testosterone had inverse independent correlations with CSF α-synuclein and right globus pallidus volume. FSH and LH had age-dependent correlations with cognitive impairment and CSF amyloid-ß-42/amyloid-ß-40 ratio. CONCLUSIONS: The study suggested that sex hormones could differentially contribute to clinical-pathological features of PD in male patients. Whereas estradiol might have a protective role in motor impairment, testosterone might be involved in male vulnerability to PD neuropathology. Gonadotropins instead might mediate age-dependent phenomena of amyloidopathy and cognitive decline.

Bithalamic infarction in a tentorial dural artero-venous fistula and thalamic dementia: a case report and systematic review.

PURPOSE: To report a case of bilateral thalamic infarction (BTI) presenting as progressive thalamic dementia due to a midline tentorial dAVF (TdAVF) and to provide a systematic review of the literature. METHODS: We performed a systematic literature review of previously reported cases of bi-thalamic signal changes due to dAVF considering population characteristics, clinical presentation, imaging findings, treatments, and outcomes. RESULTS: We found 29 papers from 1985 until 2021 describing 35 cases of BTI dAVF-related. We analysed 36 cases comprehensive of our case report. The mean age was 58.7 years (range 38-79), 91.6% were males (n=33). Most cases presented with a subacute syndrome. In 86.1% (n=31) of cases a TdAVF was found; 58.3% (n=21) were type 2 Borden-Shucart fistulas, the remaining were mostly type 3. In 80.5% (n=29), a thrombosed sinus was identified. 33.3% of cases (n=12) had bi-thalamic haemorrhages. Endovascular treatment was performed in 83.3% of cases (n=30). A total of 75% (n=27) of cases had a good recovery. CONCLUSIONS: BTIs due to dAVFs may present with subacute symptoms overlapping with several differential diagnoses. Prompt identification at MRI, before venous drainage failure and bleeding, is crucial for a good prognosis.

Global and local brain connectivity changes associated with sudden unilateral sensorineural hearing loss.

Recent studies suggest that even moderate sudden sensorineural hearing loss (SSNHL) causes reduction of gray matter volume in the primary auditory cortex, diminishing its ability to react to sound stimulation, as well as reorganization of functional brain networks. We employed resting-state functional MRI (rs-fMRI), in conjunction with graph-theoretical analysis and a newly developed functional "disruption index," to study whole-brain as well as local functional changes in patients with unilateral SSNHL. We also assessed the potential of graph-theoretical measures as biomarkers of disease, in terms of their relationship to clinically relevant audiological parameters. Eight patients with moderate or severe unilateral SSNHL and 15 healthy controls were included in this prospective pilot study. All patients underwent rs-fMRI to study potential changes in brain connectivity. From rs-fMRI data, global and local graph-theoretical measures, disruption index, and audiological examinations were estimated. Mann-Whitney U tests were used to study the differences between SSNHL patients and healthy controls. Associations between brain metrics and clinical variables were studied using multiple linear regressions, and the presence or absence of brain network hubs was assessed using Fisher's exact test. No statistically significant differences between SSNHL patients and healthy controls were found in global or local network measures. However, when analyzing brain networks through the disruption index, we found a brain-wide functional network reorganization (p < 0.001 as compared with controls), whose extent was associated with clinical impairment (p < 0.05). We also observed several functional hubs in SSNHL patients that were not present in healthy controls and vice versa. Our results demonstrate a brain involvement in SSNHL patients, not detectable using conventional graph-theoretical analysis, which may yield subtle disease clues and possibly aid in monitoring disease progression in clinical trials.

Neuroimaging findings in leukoencephalopathy with calcifications and cysts: case report and review of the literature.

Leukoencephalopathy with cerebral calcifications and cysts (LCC) is a neurological disorder characterized by the radiological triad of white matter abnormalities, intracranial calcifications and cystic lesions variable in size resulting from a diffuse cerebral microangiopathy. Typically, progressive focal neurological deficits and seizures are the first clinical manifestation, but the severity of symptoms can vary according to the size and location of the cystic lesions holding compressive effects on the surrounding brain tissue. The most common histopathological finding is diffuse microangiopathy, which might be associated to pathogenic mutations in SNORD118 gene causing Labrune syndrome. Similar neuroradiological appearances have been found in the Coats plus syndrome, a systemic disorder caused by a genetic diffuse microangiopathy that affects not only the brain but also the retina and multiple organs, with a more complex clinical picture that address the diagnosis; biallelic mutations in CTC1 gene, encoding the conserved telomere maintenance component 1 (CTC1), are responsible of this systemic disorder. The aim of this contribution is to review the existing literature focusing on the neuroimaging characteristics by reporting cases in which radiological findings were highly suggestive for LCC.

Qualitative and quantitative analysis of 3D T1 Silent imaging.

PURPOSE: To compare brain magnetic resonance imaging (MRI) using T1 3D Silent and fast T1 3D Gradient-Echo (GRE) BRAin VOlume (known as BRAVO) sequences. The primary aim is to assess the quantitative and qualitative analysis of Silent and BRAVO images by the measurement of the contrast (C), the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR). The second aim is to estimate the subjective sound levels and the specific absorption rate (SAR). METHODS: Twenty-two subjects had T1 3D Silent and T1 3D BRAVO sequences added to the standard MR examination. The qualitative analysis of the two sequences was performed by two radiologists independently. The quantitative analysis was performed by placing regions of interest on the cerebrospinal fluid, on the white and grey matter. The C, the CNR and the SNR were calculated for each sequence. After each T1-3D sequence, subjects gave a score rating to evaluate the acoustic noise. Finally, the SAR was evaluated by the digital imaging and communications in medicine (DICOM) tags. RESULTS: The image quality scores obtained by the two radiologists were higher for BRAVO compared to the Silent. However, qualitatively, the Silent images were similar to BRAVO for diagnostic use. Quantitatively, CNR for GM-CSF was comparable in the two sequences and SNR in CSF was higher in Silent than BRAVO. The acoustic noise of Silent sequence was statistically lower compared with BRAVO. The maximum SAR measured was 1.4 W/kg. CONCLUSIONS: 3D T1 Silent can be a valid alternative technique to conventional BRAVO to reduce the acoustic noise preserving the diagnostic accuracy. However, radiologists preferred the conventional sequence to Silent.

Radiological imaging in multiple myeloma: review of the state-of-the-art.

PURPOSE: Multiple myeloma is a type of blood cancer arising from the uncontrolled clonal proliferation of malignant plasma cells resulting in impaired hematopoiesis, hyper production of monoclonal protein, bone tissue destruction leading and renal system alterations up to kidney failure. The aim is to review the state-of-the-art of radiological imaging in multiple myeloma. METHODS: Radiological techniques as well as the advancements in imaging technology have been reviewed and summarized. The main radiological findings of different imaging techniques in patients suffering from multiple myeloma are also illustrated. RESULTS: Different radiological techniques provide structural and functional data. In the last years, conventional skeletal survey has gradually lost its utility and it has been replaced by whole body low-dose computed tomography which allows to identify also small lytic lesions, the medullary and the extramedullary involvement. Nowadays, magnetic resonance is the most sensitive imaging technique for detecting of skeletal as well as medullary involvement in patients with multiple myeloma. Thanks to the multiparametric evaluation (morphological, diffusion weighted and perfusion imaging sequences) and to the quantitative analysis, magnetic resonance imaging is proved to be useful in the early evaluation of response to therapy. Finally, positron emission tomography has greater sensibility compared to computed tomography as it provides quantitative data; however, the lower expression levels of the specific gene involved in the glycolysis pathway are associated with false-negative results with consequent underestimation of the disease. CONCLUSION: The only use of the advanced combined multimodal imaging allows a better evaluation, staging and early assessment of treatment response in patients with multiple myeloma.

Comparison between synthetic and conventional magnetic resonance imaging in patients with multiple sclerosis and controls.

OBJECTIVES: Synthetic magnetic resonance imaging (SyMRI) allows to obtain different weighted-images using the multiple-dynamic multiple-echo sequence lasting 6 min. The aim is to compare quantitatively and qualitatively synthetic- and conventional MRI in patients with multiple sclerosis (MS) and controls assessing the contrast (C), the signal to noise ratio (SNR), and the contrast to noise ratio (CNR). We evaluated the lesion count and lesion-to-white matter contrast ([Formula: see text] in the MS patients. METHODS AND METHODS: 51 patients underwent synthetic- and conventional MRI. Qualitative analysis was evaluated by assigning scores to all synthetic- and conventional MRI sequences by two neuroradiologists. Lesions were counted in MS patients both in the conventional- and synthetic T2-FLAIR. Regions of interest were placed in the cerebrospinal fluid, in the white- and grey matter. For the sequences were evaluated: C, CNR, and SNR. RESULTS: Synthetic T2-FLAIR images are qualitatively inferior. C and CNR were significantly higher in synthetic T1W and T2W images compared to conventional images, but not for T2-FLAIR. The SNR value was always lower in synthetic images than in conventional ones. CONCLUSIONS: SyMRI can be used in clinical practice because it has a similar diagnostic accuracy which reduces the scanning time compared to the conventional one. However, synthetic T2-FLAIR images need to be improved.

Abnormal cervical lymph nodes in multiple sclerosis: a preliminary ultrasound study.

BACKGROUND: Cervical lymph nodes are the first drainage stations of the brain and therefore play a key role in neuroinflammatory disorders such as multiple sclerosis. OBJECTIVE: The aim of this study was to evaluate, by using ultrasound imaging, cervical lymph nodes in patients with multiple sclerosis and to ascertain if such patients have any clinical features to attest their role. METHODS: We enrolled 43 patients affected by relapsing-remitting multiple sclerosis (22 drug free and 21 under treatment with natalizumab or fingolimod), who underwent ultrasound examination. The morphology, diameters and volume of cervical lymph nodes were measured. We evaluated also a control group of 20 healthy volunteers. RESULTS: Between-group comparisons showed that the mean anteroposterior diameters in the cervical lymph nodes on both sides of the neck were significantly different (χ 2 = 19.5, p < 0.001 for right; χ 2 = 20.0, p < 0.001 for left). Post hoc contrasts showed that the mean anteroposterior diameters were greater both in drug-naive (mean ± SD 0.66 ± 0.20 cm; p < 0.001) and treated patients (0.55 ± 0.24 cm; p < 0.001) compared to healthy individuals (0.36 ± 0.19 cm). Moreover, significant difference (p < 0.001) was shown on comparing the mean volume of the cervical lymph nodes on both sides of the neck in the studied groups. No significant differences emerged between the drug-free and treated patients. CONCLUSION: The abnormalities shown by ultrasound in cervical lymph nodes are related to deep ones and independent of the ongoing treatment, suggesting a relationship between lymphatic drainage and disease pathology.

Cerebritis, optic ischemia, and cavernous sinus thrombosis arising from sinonasal mucormycosis.

Brain and ocular infections can be the worst and fatal consequences of sinonasal infections in immunomodulated or immunocompromised patients. We report a case of a 35-year-old female who received an allogenic hematopoietic stem cell transplantation for acute myeloid leukemia, suffering from maxillo-spheno-ethmoidal rhinosinusitis which was complicated by cavernous sinus thrombosis, orbital cellulitis, optic ischemia and cerebritis.

Influence of scan duration on dynamic contrast -enhanced magnetic resonance imaging pharmacokinetic parameters for brain lesions.

OBJECTIVE: Gadolinium-based contrast agent needs time to leak into the extravascular-extracellular space, leak back into the vascular space, and reach an equilibrium state. For this reason, acquisition times of <10 min may cause inaccurate estimation of pharmacokinetic parameters. Since no studies have been conducted on the influence of long scan times on DCE-MRI parameters in brain tumors, the aim of this study is to investigate the variation of DCE-MRI-derived kinetic parameters as a function of acquisition time, from 5 to 10 min in brain tumors. MATERIALS AND METHODS: Fifty-two patients with histologically confirmed brain tumors were enrolled in this retrospective study, and examination at 3 T, DCE-MRI, with scan duration of 10 min, was used for retrospective generation of 6 sets of quantitative DCE-MRI maps (Ktrans, Ve and Kep) from 5 to 10 min. Features were extracted from the DCE-MRI maps in contrast enhancement (CE) volumes. Kruskal-Wallis with post-hoc correction and coefficient of variation (CoV) were used as statistical test to compare DCE-MRI maps obtained from 6 data sets. SIGNIFICANCE: p < 0.05. RESULTS: No differences in Ktrans features in CE volumes between different scan durations. Ve, Kep features in CE volumes were influenced by different data length. The highest number of significantly different Ve and Kep features in CE volumes were between 5 min and 10 min (p < 0.013), 5 min and 9 min (p < 0.044), 6 min and 10 min (p < 0.040). CoV of Kep was reduced from 5 min to 10 min, going from highly variable (CoV = 0.70) to mildly variable (CoV = 0.42). CONCLUSION: Kep and Ve were time-dependent in brain tumors, so a longer scan time is needed to obtain reliable parameter values. Ktrans was found to be time-independent, as it remains the same in all 6 acquisition times and is the only reliable parameter with short acquisition times.

Cardiac lipoma of the interventricular septum presenting with chest pain.

In this case report, we describe an incidental finding of interventricular septum lipoma in a 55-year-old man who came to our attention for chest pain. The ECG showed no changes compatible with ongoing ischemia. While laboratory tests documented increased troponin levels with normal D-dimer levels. Due to the technical difficulties encountered during the performance of the transthoracic echocardiogram, a cardiac CT scan was requested, which ruled out significant coronary artery disease and acute aortic syndromes and showed the presence of a circumscribed fat-dense mass located in the basal portion of the interventricular septum. Subsequent cardiac MRI confirmed the diagnosis of lipoma of the interventricular septum.

Triple gallbladder: radiological review.

Triple gallbladder represents a rare congenital anatomical abnormality that can be a diagnostic challenge in reason to its rarity and consequential difficulties with diagnosis and identification. A systematic review of all published literature between 1958 and 2022 was performed. We identified 20 previous studies that provided 20 cases of triple gallbladder; our case was also included in the analysis, making a total of 21 patients. All patients underwent on diagnostic imaging examinations. After 1985, 9 patients underwent US examination which allowed prompt recognition of triple gallbladder in 2 patients only. CT was performed in 3 patients and allowed the correct diagnosis in a case. In 4 patients, was performed MRCP which allowed the correct diagnosis of triple gallbladder in all patients. Preoperative imaging allows the recognition of triple gallbladder in 9 of 21 patients (43%); in 12 patients (57%) the diagnosis was intraoperative. On patients considered, 16/21 underwent cholecystectomy. In 15 cases, the excised gallbladders were submitted for histopathological characterization with detection of metaplasia of the mucosa in 3 patients, while papillary adenocarcinoma was found in one. Imaging plays a key role in the identification of the anatomical variants of gallbladder, especially triple gallbladder, as modern imaging techniques allow a detailed assessment of the course of the biliary tract for a correct preoperative diagnosis. It is also crucial to be aware of the association between this condition and the metaplasia phenomena with the development of adenocarcinoma, as this may influence the patient's course of treatment.

Clinical and functional characterization of COL2A1 p.Gly444Ser variant: From a fetal phenotype to a previously undisclosed postnatal phenotype.

COL2A1 gene encodes the alpha-1 chain of type-II procollagen. Heterozygous pathogenic variants are associated with the broad clinical spectrum of genetic diseases known as type-II collagenopathies. We aimed to characterize the NM_001844.5:c.1330G>A;p.Gly444Ser variant detected in the COL2A1 gene through trio-based prenatal exome sequencing in a fetus presenting a severe skeletal phenotype at 31 Gestational Weeks and in his previously undisclosed mild-affected father. Functional studies on father's cutaneous fibroblasts, along with in silico protein modeling and in vitro chondrocytes differentiation, showed intracellular accumulation of collagen-II, its localization in external Golgi vesicles and nuclear morphological alterations. Extracellular matrix showed a disorganized fibronectin network. These results showed that p.Gly444Ser variant alters procollagen molecules processing and the assembly of mature type-II collagen fibrils, according to COL2A1-chain disorganization, displayed by protein modeling. Clinical assessment at 38 y.o., through a reverse-phenotyping approach, revealed limp gait, short and stocky appearance. X-Ray and MRI showed pelvis asymmetry with severe morpho-structural alterations of the femoral heads bilaterally, consistent with a mild form of type-II collagenopathy. This study shows how the fusion of genomics and clinical expertise can drive a diagnosis supported by cellular and bioinformatics studies to effectively establish variants pathogenicity.

Imaging biomarkers for Alzheimer's disease and glaucoma: Current and future practices.

Glaucoma is a leading cause of blindness worldwide. Although intraocular pressure is the main risk factor for glaucoma, several intraocular pressure independent factors have been associated with the risk of developing the disease and its progression. The diagnosis of glaucoma relies on clinical features of the optic nerve, visual field test, and optical coherence tomography. However, the multidisciplinary aspect of the disease suggests that other biomarkers may be useful for the diagnosis, thus underling the importance of novel imaging techniques supporting clinicians. This review analyzes the common pathogenic mechanisms between glaucoma and Alzheimer's disease and the possible novel approaches for diagnosis and follow up.

Coexistence of primary central nervous system lymphoma and primary breast lymphoma: Clinical presentation, imaging features, and treatment management.

The presence of synchronous dual hematological diseases is an uncommon finding. We report an unusual case of coexistence of primary central nervous system lymphoma and primary breast lymphoma without systemic involvement in an immunocompetent patient. To our knowledge a similar case has not yet been reported in the literature. We especially focus on presenting the imaging features, the associated clinical findings and treatment management of each entity, with the aim of raising awareness on these two rare types of lymphomas and the possibility of their coexistence.

Spinal vascular lesions: anatomy, imaging techniques and treatment.

BACKGROUND: Vascular lesions of the spinal cord are rare but potentially devastating conditions whose accurate recognition critically determines the clinical outcome. Several conditions lead to myelopathy due to either arterial ischemia, venous congestion or bleeding within the cord. The clinical presentation varies, according with the different aetiology and mechanism of damage. PURPOSE: The aim is to provide a comprehensive review on the radiological features of the most common vascular myelopathies, passing through the knowledge of the vascular spinal anatomy and the clinical aspects of the different aetiologies, which is crucial to promptly address the diagnosis and the radiological assessment.

Compartmental models for diffusion weighted MRI reveal widespread brain changes in HIV-infected patients.

Diffusion tensor imaging (DTI) has been used to explore changes in the brain of subjects with human immunodeficiency virus (HIV) infection. However, DTI notoriously suffers from low specificity. Neurite orientation dispersion and density imaging (NODDI) is a compartmental model able to provide specific microstructural information with additional sensitivity/specificity. In this study we use both the NODDI and the DTI models to evaluate microstructural differences between 35 HIV-positive patients and 20 healthy controls. Diffusion-weighted imaging was acquired using three b-values (0, 1000 and 2500 s/mm2). Both DTI and NODDI models were fitted to the data, obtaining estimates for fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), neurite density index (NDI) and orientation dispersion index (ODI), after which we performed group comparisons using Tract-based spatial statistics (TBSS). While significant group effects were found in in FA, MD, RD, AD and NDI, NDI analysis uncovered a much wider involvement of brain tissue in HIV infection as compared to DTI. In region-of interest (ROI)-based analysis, NDI estimates from the right corticospinal tract produced excellent performance in discriminating the two groups (AUC = 0.974, sensitivity = 90%; specificity =97%).

Functional brain network reorganization in HIV infection.

BACKGROUND AND PURPOSE: To investigate the reorganization of the central nervous system provided by resting state-functional MRI (rs-fMRI), graph-theoretical analysis, and a newly developed functional brain network disruption index in patients with human immunodeficiency virus (HIV) infection. METHODS: Forty HIV-positive patients without neurological impairment and 20 age- and sex-matched healthy controls underwent rs-fMRI at 3T; blood sampling was obtained the same day to evaluate biochemical variables (absolute, relative, and nadir CD4 T-lymphocytes value and plasmatic HIV-RNA). From fMRI data, disruption indices, as well as global and local graph theoretical measures, were estimated and examined for group differences (HIV vs. controls) as well as for associations with biochemical variables (HIV only). Finally, all data (global and local graph-theoretical measures, disruption indices, and biochemical variables) were tested for putative differences across three patient groups based on the duration of combined antiretroviral therapy (cART). RESULTS: Brain function of HIV patients appeared to be deeply reorganized as compared to normal controls. The disruption index showed significant negative association with relative CD4 values, and a positive significant association between plasmatic HIV-RNA and local graph-theoretical metrics in the left lingual gyrus and the right lobule IV and V of right cerebellar hemisphere was also observed. Finally, a differential distribution of HIV clinical biomarkers and several brain metrics was observed across cART duration groups. CONCLUSION: Our study demonstrates that rs-fMRI combined with advanced graph theoretical analysis and disruption indices is able to detect early and subtle functional changes of brain networks in HIV patients.

Diffusional Kurtosis Imaging of White Matter Degeneration in Glaucoma.

Glaucoma is an optic neuropathy characterized by death of retinal ganglion cells and loss of their axons, progressively leading to blindness. Recently, glaucoma has been conceptualized as a more diffuse neurodegenerative disorder involving the optic nerve and also the entire brain. Consistently, previous studies have used a variety of magnetic resonance imaging (MRI) techniques and described widespread changes in the grey and white matter of patients. Diffusion kurtosis imaging (DKI) provides additional information as compared with diffusion tensor imaging (DTI), and consistently provides higher sensitivity to early microstructural white matter modification. In this study, we employ DKI to evaluate differences among healthy controls and a mixed population of primary open angle glaucoma patients ranging from stage I to V according to Hodapp-Parrish-Anderson visual field impairment classification. To this end, a cohort of patients affected by primary open angle glaucoma (n = 23) and a group of healthy volunteers (n = 15) were prospectively enrolled and underwent an ophthalmological evaluation followed by magnetic resonance imaging (MRI) using a 3T MR scanner. After estimating both DTI indices, whole-brain, voxel-wise statistical comparisons were performed in white matter using Tract-Based Spatial Statistics (TBSS). We found widespread differences in several white matter tracts in patients with glaucoma relative to controls in several metrics (mean kurtosis, kurtosis anisotropy, radial kurtosis, and fractional anisotropy) which involved localization well beyond the visual pathways, and involved cognitive, motor, face recognition, and orientation functions amongst others. Our findings lend further support to a causal brain involvement in glaucoma and offer alternative explanations for a number of multidomain impairments often observed in glaucoma patients.