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.

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.

Detection of Hippocampal Subfield Asymmetry at 7T With Automated Segmentation in Epilepsy Patients With Normal Clinical Strength MRIs.

While the etiology of hippocampal sclerosis (HS) in epilepsy patients remains unknown, distinct phenotypes of hippocampal subfield atrophy have been associated with different clinical presentations and surgical outcomes. The advent of novel techniques including ultra-high field 7T magnetic resonance imaging (MRI) and automated subfield volumetry have further enabled detection of hippocampal pathology in patients with epilepsy, however, studies combining both 7T MRI and automated segmentation in epilepsy patients with normal-appearing clinical MRI are limited. In this study, we present a novel application of the automated segmentation of hippocampal subfields (ASHS) software to determine subfield volumes of the CA1, CA2/3, CA4/DG, and the subiculum using ultra high-field 7T MRI scans, including T1-weighted MP2RAGE and T2-TSE sequences, in 27 patients with either mesial temporal lobe epilepsy (mTLE) or neocortical epilepsy (NE) compared to age and gender matched healthy controls. We found that 7T improved visualization of structural abnormalities not otherwise seen on clinical strength MRIs in patients with unilateral mTLE. Additionally, our automated segmentation algorithm was able to detect structural differences in volume and asymmetry across hippocampal subfields in unilateral mTLE patients compared to controls. Specifically, amongst unilateral mTLE patients with longer disease durations, volume loss was observed in the ipsilateral CA1 and CA2/3 subfields and contralateral CA1. There were no differences in subfield volumes in patients with NE compared to controls. We report the first application of 7T with automated segmentation to characterize the relationship between disease duration burden and asymmetry across specific hippocampal subfields in this population. Disease duration was found to have a statistically significant positive relationship with subfield asymmetry within the unilateral mTLE cohort. These findings highlight the ability of 7T MRI and automated segmentation to provide novel qualitative and quantitative information in epilepsy patients who are otherwise MRI-negative at clinical field strengths.

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.

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.

Is There a Magnetic Resonance Imaging-Discernible Cause for Trigeminal Neuralgia? A Structured Review.

BACKGROUND: Trigeminal neuralgia (TN) is a chronic brain condition involving the trigeminal nerve and characterized by severe and recurrent facial pain. Although the cause of TN has been researched extensively, there is a lack of convergence on the physiologic processes leading to pain symptoms. This review seeks to better elucidate the underlying pathophysiology of TN by analyzing the outcomes of studies that use magnetic resonance structural imaging and diffusion-weighted imaging to examine nerve damage in patients with TN. METHODS: Performing a structured review of the literature, the authors included human magnetic resonance anatomic and diffusion-weighted imaging studies aimed at visualizing the trigeminal nerve or measuring neural damage pertaining to TN. Studies that measured and compared nerve damage in the affected and unaffected sides in patients or patients and controls were analyzed for neural changes associated with TN. RESULTS: Twenty-five studies met inclusion criteria. Overall, the data from the anatomic and diffusion studies showed decreased volume and cross-sectional area, decreased fractional anisotropy, and increased apparent diffusion coefficient and diffusivity associated with the affected side of patients compared with the unaffected side as well as in patients compared with controls. CONCLUSIONS: A review of the studies included indicates that neural differences exist between the affected and unaffected sides in patients as well as between patients and controls in both structural and diffusion metrics. The amalgamated data suggest that damage of the trigeminal nerve tissue is commonly found in patients with TN and could be a primary factor in TN pathophysiology.