Stress-related reduction of hippocampal subfield volumes in major depressive disorder: A 7-Tesla study.

Background: Major depressive disorder (MDD) is a prevalent health problem with complex pathophysiology that is not clearly understood. Prior work has implicated the hippocampus in MDD, but how hippocampal subfields influence or are affected by MDD requires further characterization with high-resolution data. This will help ascertain the accuracy and reproducibility of previous subfield findings in depression as well as correlate subfield volumes with MDD symptom scores. The objective of this study was to assess volumetric differences in hippocampal subfields between MDD patients globally and healthy controls (HC) as well as between a subset of treatment-resistant depression (TRD) patients and HC using automatic segmentation of hippocampal subfields (ASHS) software and ultra-high field MRI. Methods: Thirty-five MDD patients and 28 HC underwent imaging using 7-Tesla MRI. ASHS software was applied to the imaging data to perform automated hippocampal segmentation and provide volumetrics for analysis. An exploratory analysis was also performed on associations between symptom scores for diagnostic testing and hippocampal subfield volumes. Results: Compared to HC, MDD and TRD patients showed reduced right-hemisphere CA2/3 subfield volume (p = 0.01, η 2 = 0.31 and p = 0.3, η 2 = 0.44, respectively). Additionally, negative associations were found between subfield volumes and life-stressor checklist scores, including left CA1 (p = 0.041, f 2 = 0.419), left CA4/DG (p = 0.010, f 2 = 0.584), right subiculum total (p = 0.038, f 2 = 0.354), left hippocampus total (p = 0.015, f 2 = 0.134), and right hippocampus total (p = 0.034, f 2 = 0.110). Caution should be exercised in interpreting these results due to the small sample size and low power. Conclusion: Determining biomarkers for MDD and TRD pathophysiology through segmentation on high-resolution MRI data and understanding the effects of stress on these regions can enable better assessment of biological response to treatment selection and may elucidate the underlying mechanisms of depression.

Lateralisation of subcortical functional connectivity during and after general anaesthesia.

BACKGROUND: Arousal and awareness are two important components of consciousness states. Functional neuroimaging has furthered our understanding of cortical and thalamocortical mechanisms of awareness. Investigating the relationship between subcortical functional connectivity and arousal has been challenging owing to the relatively small size of brainstem structures and thalamic nuclei, and their depth in the brain. METHODS: Resting state functional MRI scans of 72 healthy volunteers were acquired before, during, 1 h after, and 1 day after sevoflurane general anaesthesia. Functional connectivity of subcortical regions of interest vs whole brain and homotopic functional connectivity for assessment of left-right symmetry analyses of both cortical and subcortical regions of interest were performed. Both analyses used high resolution atlases generated from deep brain stimulation applications. RESULTS: Functional connectivity in subcortical loci within the thalamus and of the ascending reticular activating system was sharply restricted under anaesthesia, featuring a general lateralisation of connectivity. Similarly, left-right homology was sharply reduced under anaesthesia. Subcortical bilateral functional connectivity was not fully restored after emergence from anaesthesia, although greater restoration was seen between ascending reticular activating system loci and specific thalamic nuclei thought to be involved in promoting and maintaining arousal. Functional connectivity was fully restored to baseline by the following day. CONCLUSIONS: Functional connectivity in the subcortex is sharply restricted and lateralised under general anaesthesia. This restriction may play a part in loss and return of consciousness. CLINICAL TRIAL REGISTRATION: NCT02275026.

Leveraging high-resolution 7-tesla MRI to derive quantitative metrics for the trigeminal nerve and subnuclei of limbic structures in trigeminal neuralgia.

BACKGROUND: Trigeminal Neuralgia (TN) is a chronic neurological disease that is strongly associated with neurovascular compression (NVC) of the trigeminal nerve near its root entry zone. The trigeminal nerve at the site of NVC has been extensively studied but limbic structures that are potentially involved in TN have not been adequately characterized. Specifically, the hippocampus is a stress-sensitive region which may be structurally impacted by chronic TN pain. As the center of the emotion-related network, the amygdala is closely related to stress regulation and may be associated with TN pain as well. The thalamus, which is involved in the trigeminal sensory pathway and nociception, may play a role in pain processing of TN. The objective of this study was to assess structural alterations in the trigeminal nerve and subregions of the hippocampus, amygdala, and thalamus in TN patients using ultra-high field MRI and examine quantitative differences in these structures compared with healthy controls. METHODS: Thirteen TN patients and 13 matched controls were scanned at 7-Tesla MRI with high resolution, T1-weighted imaging. Nerve cross sectional area (CSA) was measured and an automated algorithm was used to segment hippocampal, amygdaloid, and thalamic subregions. Nerve CSA and limbic structure subnuclei volumes were compared between TN patients and controls. RESULTS: CSA of the posterior cisternal nerve on the symptomatic side was smaller in patients (3.75 mm2) compared with side-matched controls (5.77 mm2, p = 0.006). In TN patients, basal subnucleus amygdala volume (0.347 mm3) was reduced on the symptomatic side compared with controls (0.401 mm3, p = 0.025) and the paralaminar subnucleus volume (0.04 mm3) was also reduced on the symptomatic side compared with controls (0.05 mm3, p = 0.009). The central lateral thalamic subnucleus was larger in TN patients on both the symptomatic side (0.033 mm3) and asymptomatic side (0.035 mm3), compared with the corresponding sides in controls (0.025 mm3 on both sides, p = 0.048 and p = 0.003 respectively). The inferior and lateral pulvinar thalamic subnuclei were both reduced in TN patients on the symptomatic side (0.2 mm3 and 0.17 mm3 respectively) compared to controls (0.23 mm3, p = 0.04 and 0.18 mm3, p = 0.04 respectively). No significant findings were found in the hippocampal subfields analyzed. CONCLUSIONS: These findings, generated through a highly sensitive 7 T MRI protocol, provide compelling support for the theory that TN neurobiology is a complex amalgamation of local structural changes within the trigeminal nerve and structural alterations in subnuclei of limbic structures directly and indirectly involved in nociception and pain processing.

Fully automated prediction of liver fibrosis using deep learning analysis of gadoxetic acid-enhanced MRI.

OBJECTIVES: To (1) develop a fully automated deep learning (DL) algorithm based on gadoxetic acid-enhanced hepatobiliary phase (HBP) MRI and (2) compare the diagnostic performance of DL vs. MR elastography (MRE) for noninvasive staging of liver fibrosis. METHODS: This single-center retrospective study included 355 patients (M/F 238/117, mean age 60 years; training, n = 178; validation, n = 123; test, n = 54) who underwent gadoxetic acid-enhanced abdominal MRI, including HBP and MRE, and pathological evaluation of the liver within 1 year of MRI. Cropped liver HBP images from a custom-written fully automated liver segmentation were used as input for DL. A transfer learning approach based on the ImageNet VGG16 model was used. Different DL models were built for the prediction of fibrosis stages F1-4, F2-4, F3-4, and F4. ROC analysis was performed to evaluate the performance of DL in training, validation, and test sets and of MRE liver stiffness in the test set. RESULTS: AUC values of DL were 0.99/0.70/0.77 (F1-4), 0.92/0.71/0.91 (F2-4), 0.91/0.78/0.90 (F3-4), and 0.98/0.83/0.85 (F4) for training/validation/test sets, respectively. The AUCs of MRE liver stiffness in the test set were 0.86 (F1-4), 0.87 (F2-4), 0.92 (F3-4), and 0.86 (F4). AUCs of MRE and DL were not significantly different for any of the fibrosis stages (p > 0.134). CONCLUSIONS: The fully automated DL models based on HBP gadoxetic acid MRI showed good-to-excellent diagnostic performance for staging of liver fibrosis, with similar diagnostic performance to MRE. After validation in independent sets, the DL algorithm may allow for noninvasive liver fibrosis assessment without the need for additional MRI hardware. KEY POINTS: • The developed deep learning algorithm, based on routine standard-of-care gadoxetic acid-enhanced MRI data, showed good-to-excellent diagnostic performance for noninvasive staging of liver fibrosis. • The diagnostic performance of the deep learning algorithm was equivalent to that of MR elastography in a separate test set.

Resting-state functional connectivity in early postanaesthesia recovery is characterised by globally reduced anticorrelations.

BACKGROUND: A growing body of literature addresses the possible long-term cognitive effects of anaesthetics, but no study has delineated the normal trajectory of neural recovery attributable to anaesthesia alone in adults. We obtained resting-state functional MRI scans on 72 healthy human volunteers between ages 40 and 80 (median: 59) yr before, during, and after general anaesthesia with sevoflurane, in the absence of surgery, as part of a larger study on cognitive function postanaesthesia. METHODS: Region-of-interest analysis, independent component analysis, and seed-to-voxel analysis were used to characterise resting-state functional connectivity and to differentiate between correlated and anticorrelated connectivity before, during, and after general anaesthesia. RESULTS: Whilst positively correlated functional connectivity remained essentially unchanged across these perianaesthetic states, anticorrelated functional connectivity decreased globally by 35% 1 h after emergence from general anaesthesia compared with baseline, as seen by the region-of-interest analysis. This decrease corresponded to a consistent reduction in expression of canonical resting-state networks, as seen by independent component analysis. All measures returned to baseline 1 day later. CONCLUSIONS: The normal perianaesthesia trajectory of resting-state connectivity in healthy adults is characterised by a transient global reduction in anticorrelated activity shortly after emergence from anaesthesia that returns to baseline by the following day. CLINICAL TRIAL REGISTRATION: NCT02275026.

Neural correlates of rumination in major depressive disorder: A brain network analysis.

Patients with major depressive disorder (MDD) exhibit higher levels of rumination, i.e., repetitive thinking patterns and exaggerated focus on negative states. Rumination is known to be associated with the cortical midline structures / default mode network (DMN) region activity, although the brain network topological organization underlying rumination remains unclear. Implementing a graph theoretical analysis based on ultra-high field 7-Tesla functional MRI data, we tested whether whole brain network connectivity hierarchies during resting state are associated with rumination in a dimensional manner across 20 patients with MDD and 20 healthy controls. Applying this data-driven approach we found a significant correlation between rumination tendency and connectivity strength degree of the right precuneus, a key node of the DMN. In order to interrogate this region further, we then applied the Dependency Network Analysis (DEPNA), a recently developed method used to quantify the connectivity influence of network nodes. This revealed that rumination was associated with lower connectivity influence of the left medial orbito-frontal cortex (MOFC) cortex on the right precuneus. Lastly, we used an information theory entropy measure that quantifies the cohesion of a network's correlation matrix. We show that subjects with higher rumination scores exhibit higher entropy levels within the DMN i.e. decreased overall connectivity within the DMN. These results emphasize the general DMN involvement during self-reflective processing related to maladaptive rumination in MDD. This work specifically highlights the impact of the MOFC on the precuneus, which might serve as a target for clinical neuromodulation treatment.

Neuroanatomical Determinants of Secondary Trigeminal Neuralgia: Application of 7T Ultra-High-Field Multimodal Magnetic Resonance Imaging.

BACKGROUND: Seven-Tesla (7T) magnetic resonance imaging (MRI) has demonstrated value for evaluating a variety of intracranial diseases. However, its utility in trigeminal neuralgia has received limited attention. The authors of the present study applied ultra-high field multimodal MRI to two representative patients with secondary trigeminal neuralgia due to epidermoid tumors to illustrate the possible clinical and surgical advantages of 7T compared with standard clinical strength imaging. Techniques included co-registration of multiple 7T sequences to optimize the detection of potential concurrent neurovascular and neoplasm-derived compression. METHODS: 7T MRI studies were performed using a whole body scanner. Two- and three-dimensional renderings of potential neurovascular conflict were created by co-registering time-of-flight angiography and T2-weighted turbo spin echo images in MATLAB and GE software. Detailed comparisons of the various field strength images were provided by a collaborating neuroradiologist (B.D.). RESULTS: 7T MRI clearly illustrated minute tumor-adjacent vasculature. In contrast, conventional, low-field imaging did not consistently provide adequate details to distinguish cerebrospinal fluid pulsatility from vessels. The tumor margins, although distinct from the trigeminal nerve fibers at 7T, blended with those of the surrounding structures at 3T. Two- and three-dimensional co-registration of time-of-flight angiography with T2-weighted MRI suggested that delicate, intervening vasculature may have contributed to these illustrative patients' symptomatology. CONCLUSIONS: 7T provided superior visualization of vital landmarks and subtle nerve and vessel features. Co-registration of various advanced 7T modalities may help to resolve complex disease etiologies. Future studies should explore the extent to which this dual etiology might persist across tumor types and utilize diffusion-based techniques to quantify what microstructural differences might exist between patients with trigeminal neuralgia from varying etiologies.

Primary visual cortical thickness in correlation with visual field defects in patients with pituitary macroadenomas: a structural 7-Tesla retinotopic analysis.

OBJECTIVE: Vision loss remains a debilitating complication of pituitary adenomas, although there is considerable variability in visual impairment before and after decompression surgery. Growing evidence suggests secondary damage to remote visual structures may contribute to vision loss in patients with chiasmatic compression. The present study leverages ultrahigh field 7-T MRI to study the retinotopic organization of the primary visual cortex (V1), and correlates visual defects with cortical thinning in V1 to characterize consequences of pituitary adenomas on the posterior visual system. METHODS: Eight patients (4 males and 4 females, mean age 44.3 years) with pituitary adenomas who exhibited chiasmatic compression and visual field defects, as well as 8 matched healthy controls (4 males and 4 females, mean age 43.3 years), were scanned at 7-T MRI for this prospective study. Whole-brain cortical thickness was calculated using an automated algorithm. A previously published surface-based algorithm was applied to associate the eccentricity and polar angle with each position in V1. Cortical thickness was calculated at each point in the retinotopic organization, and a cortical thickness ratio was generated against matched controls for each point in the visual fields. Patients with adenoma additionally underwent neuroophthalmological examination including 24-2 Humphrey automated visual field perimetry. Pattern deviation (PD) of each point in the visual field, i.e., the deviation in point detection compared with neurologically healthy controls, was correlated with cortical thickness at corresponding polar and eccentricity angles in V1. RESULTS: Whole-brain cortical thickness was successfully derived for all patients and controls. The mean tumor volume was 19.4 cm3. The median global thickness of V1 did not differ between patients (mean ± SD 2.21 ± 0.12 cm), compared with controls (2.06 ± 0.13 cm, p > 0.05). Surface morphometry-based retinotopic maps revealed that all 8 patients with adenoma showed a significant positive correlation between PD and V1 thickness ratios (r values ranged from 0.31 to 0.53, p < 0.05). Mixed-procedure analysis revealed that PD = -8.0719 + 5.5873*[Median V1 Thickness Ratio]. CONCLUSIONS: All 8 patients showed significant positive correlations between V1 thickness and visual defect. These findings provide retinotopic maps of localized V1 cortical neurodegeneration spatially corresponding to impairments in the visual field. These results further characterize changes in the posterior visual pathway associated with chiasmatic compression, and may prove useful in the neuroophthalmological workup for patients with pituitary macroadenoma.

First application of 7-T ultra-high field diffusion tensor imaging to detect altered microstructure of thalamic-somatosensory anatomy in trigeminal neuralgia.

OBJECTIVE: Trigeminal neuralgia (TN) is a debilitating neurological disease that commonly results from neurovascular compression of the trigeminal nerve (CN V). Although the CN V has been extensively studied at the site of neurovascular compression, many pathophysiological factors remain obscure. For example, thalamic-somatosensory function is thought to be altered in TN, but the abnormalities are inadequately characterized. Furthermore, there are few studies using 7-T MRI to examine patients with TN. The purpose of the present study was to use 7-T MRI to assess microstructural alteration in the thalamic-somatosensory tracts of patients with TN by using ultra-high field MRI. METHODS: Ten patients with TN and 10 age- and sex-matched healthy controls underwent scanning using 7-T MRI with diffusion tensor imaging. Structural images were segmented with an automated algorithm to obtain thalamus and primary somatosensory cortex (S1). Probabilistic tractography was performed between the thalamus and S1, and the microstructure of the thalamic-somatosensory tracts was compared between patients with TN and controls. RESULTS: Fractional anisotropy of the thalamic-somatosensory tract ipsilateral to the site of neurovascular compression was reduced in patients (mean 0.43) compared with side-matched controls (mean 0.47, p = 0.01). The mean diffusivity was increased ipsilaterally in patients (mean 6.58 × 10-4 mm2/second) compared with controls (mean 6.15 × 10-4 mm2/second, p = 0.02). Radial diffusivity was increased ipsilaterally in patients (mean 4.91 × 10-4 mm2/second) compared with controls (mean 4.44 × 10-4 mm2/second, p = 0.01). Topographical analysis revealed fractional anisotropy reduction and diffusivity elevation along the entire anatomical S1 arc in patients with TN. CONCLUSIONS: The present study is the first to examine microstructural properties of the thalamic-somatosensory anatomy in patients with TN and to evaluate quantitative differences compared with healthy controls. The finding of reduced integrity of these white matter fibers provides evidence of microstructural alteration at the level of the thalamus and S1, and furthers the understanding of TN neurobiology.

Quantitative assessment of secondary white matter injury in the visual pathway by pituitary adenomas: a multimodal study at 7-Tesla MRI.

OBJECTIVE: The objective of this study was to investigate microstructural damage caused by pituitary macroadenomas by performing probabilistic tractography of the optic tracts and radiations using 7-T diffusion-weighted MRI (DWI). These imaging findings were correlated with neuro-ophthalmological results to assess the utility of ultra-high-field MRI for objective evaluation of damage to the anterior and posterior visual pathways. METHODS: Probabilistic tractography employing 7-T DWI was used to reconstruct the optic tracts and radiations in 18 patients with adenomas and in 16 healthy volunteers. Optic chiasm compression was found in 66.7% of the patients and visual defects in 61.1%. Diffusion indices were calculated along the projections and correlated with tumor volumes and results from neuro-ophthalmological examinations. Primary visual cortical thicknesses were also assessed. RESULTS: Fractional anisotropy was reduced by 21.9% in the optic tracts (p < 0.001) and 17.7% in the optic radiations (p < 0.001) in patients with adenomas. Patients showed an 8.5% increase in mean diffusivity of optic radiations compared with healthy controls (p < 0.001). Primary visual cortical thickness was reduced in adenoma patients. Diffusion indices of the visual pathway showed significant correlations with neuro-ophthalmological examination findings. CONCLUSIONS: Imaging-based quantification of secondary neuronal damage from adenomas strongly correlated with neuro-ophthalmological findings. Diffusion characteristics enabled by ultra-high-field DWI may allow preoperative characterization of visual pathway damage in patients with chiasmatic compression and may inform prognosis for vision recoverability.