In vivo imaging of the nucleus of the solitary tract with Magnetization Transfer at 7 Tesla

The nucleus of the solitary tract (NTS) is a nuclei complex with, among others, a high concentration of noradrenergic neurons (including the noradrenergic subnuclei named A1 and A2) in the medulla. The NTS regulates several cognitive, neuroendocrine and autonomic functions. No method currently exists to anatomically visualize the NTS in vivo. Several noradrenergic and dopaminergic nuclei have been successfully imaged using Magnetization Transfer (MT) contrast manipulation. We therefore hypothesized that an efficient, high-resolution MT-weighted sequence at 7 T might successfully image the NTS. In this study, we found a hyperintensity, similar to hyperintensities found in other noradrenergic and dopaminergic nuclei, consistent with the expected NTS location, and specific to the MT-weighted images. The localization of the hyperintensity was found to be consistent between individuals and slices and in good correspondence to a histological atlas and a meta-analytic map of fMRI-based NTS activation. We conclude that the method may, for the first time, achieve NTS imaging in vivo and within a clinically-feasible acquisition time. To facilitate NTS research at lower field strengths, an NTS template was created and made publicly available

Neuroimaging at 7 Tesla: a pictorial narrative review

Neuroimaging using the 7-Tesla (7T) human magnetic resonance (MR) system is rapidly gaining popularity after being approved for clinical use in the European Union and the USA. This trend is the same for functional MR imaging (MRI). The primary advantages of 7T over lower magnetic fields are its higher signal-to-noise and contrast-to-noise ratios, which provide high-resolution acquisitions and better contrast, making it easier to detect lesions and structural changes in brain disorders. Another advantage is the capability to measure a greater number of neurochemicals by virtue of the increased spectral resolution. Many structural and functional studies using 7T have been conducted to visualize details in the white matter and layers of the cortex and hippocampus, the subnucleus or regions of the putamen, the globus pallidus, thalamus and substantia nigra, and in small structures, such as the subthalamic nucleus, habenula, perforating arteries, and the perivascular space, that are difficult to observe at lower magnetic field strengths. The target disorders for 7T neuroimaging range from tumoral diseases to vascular, neurodegenerative, and psychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, major depressive disorder, and schizophrenia. MR spectroscopy has also been used for research because of its increased chemical shift that separates overlapping peaks and resolves neurochemicals more effectively at 7T than a lower magnetic field. This paper presents a narrative review of these topics and an illustrative presentation of images obtained at 7T. We expect 7T neuroimaging to provide a new imaging biomarker of various brain disorders

A Study to Assess the Efficacy of Magnetization Transfer Ratio in Differentiating Tuberculoma from Neurocysticercosis.

Single Or Multiple Enhancing Lesions In Computerized Tomography (CT) Of Brain May Occur In Several Infectious And Neoplastic Diseases Of The Central Nervous System And Are The Most Common Radiological Abnormality Seen In Patients With Acute-Onset Seizures In India And Many Other Developing Countries(1,2,3,6). Similar CT-Documented Lesions Have Also Been Reported In The Developed World Where These Lesions Are Often Considered To Be Caused By Neoplasm Or Tuberculoma. (1) Histopathological Studies In India And Even In Some Developed Countries Revealed That Neurocysticercosis (NCC) Is The Most Likely Cause Of These Lesions. The Second Most Common Cause Of These CT-Detected Lesions Is Tuberculoma; In Patients With These Lesions Similar Clinical And Neuroimaging Features Are Also Present. Few Authors Believe That In Poor And Developing Countries, Where Both Tuberculosis And NCC Are Common, It Is Difficult To Differentiate Between Tuberculoma And A Single Cysticercal Granuloma. The Most Interesting Feature Of These Solitary Enhancing Lesions Is Their Spontaneous Disappearance Within Weeks Or Months. Some Lesions "Heal" By Becoming Calcified. These Patients Require Only Antiepileptic Therapy, And This Medication May Be Withdrawn Safely After The Lesion Has Resolved On CT Scanning. In Several Studies Provision Of Anticysticercal Drugs Has Been Attempted, But Because Of Conflicting Results, Their Role In The Management Of These Single Lesions Is Uncertain. (1) Using CECT And Conventional MRI Brain, Tuberculoma And Neurocysticercus Granuloma Can Be Differentiated To Some Extent.(3) Various Studies Have Shown That Magnetization Transfer Ratio Obtained Using Magnetization Transfer MR Imaging Can Differentiate Tuberculoma From NCC.(8) This Forms The Basis Of The Study

The investigation of early MRI in diagnosis and prognosis in patients presenting with a clinically isolated syndrome characteristic of demyelination

This thesis explores the use of early MRI in prognosis and diagnosis in patients presenting with a clinically isolated syndrome (CIS) characteristic of demyelination. This has been investigated in a cohort recruited within 3 months of CIS onset between 1995 and 2004 and followed up clinically and with MRI (planned at 3 months, 1,3 and 5 years). Current MRI criteria are highly specific for the development of clinically definite multiple sclerosis (CDMS) but have limited sensitivity and are complex. Presented is the evaluation of simplified MRI criteria in my London CIS cohort and in a multicentre CIS cohort. Results from the presented studies show that the MRI criteria can be simplified (dissemination in space: 2 or more lesions in separate but characteristic locations, dissemination in time: an early new T2 lesion) and still maintain high specificity, with improved sensitivity and accuracy. The prognostic role of early MRI was investigated in the optic neuritis (ON) subgroup, as 80% of my cohort presented with ON and some studies have suggested that such a presentation is associated with more benign disease. Whereas baseline lesion number significantly predicted conversion to CDMS and increased disability at 5 years, other MRI parameters, namely baseline lesion location (periventricular lesions increasing the hazard of CDMS and spinal cord and infratentorial lesions increasing the odds of greater disability at 5 years) and lesion activity (new T2 lesion at 3 month follow-up), were stronger predictors. No non-conventional MRI parameters (spectroscopy, magnetisation transfer ratio or atrophy measures) had a significant prognostic role. Overall early MRI findings can aid diagnosis and help identify the CIS patients at greatest risk of conversion to CDMS and subsequent disability, which in turn can help direct treatment and clinical follow-up in specialist MS clinics

Application of MRI Connectivity in Stereotactic Functional Neurosurgery

This thesis examines potential applications of advanced MRI-connectivity studies in stereotactic functional neurosurgery. Several new analysis methodologies are employed to: (1) build predictive models of DBS surgery outcome; (2) refine the surgical target and (3) help build a better understanding of the pathogenesis of the treated conditions and the mechanism of action of DBS therapy. The experimental component is divided into three main parts focusing on the following pathologies: (1) Parkinson’s disease (PD), (2) tremor and (3) trigeminal autonomic cephalalgias (TAC). Section I: In the first experiment (chapter 3), resting state fMRI was used to find radiological biomarkers predictive of response to L-DOPA in 19 patients undergoing subthalamic nucleus (STN) DBS for PD. A greater improvement in UPDRS-III scores following L-DOPA administration was characterized by higher resting state functional connectivity (fcMRI) between the prefrontal cortex and the striatum (p=0.001) and lower fcMRI between the pallidum (p=0.001), subthalamic nucleus (p=0.003) and the paracentral lobule. In the second experiment (chapter 4), structural (diffusion) connectivity was used to map out the influence of the hyperdirect pathways on outcome and identify the therapeutic ‘sweet spots’ in twenty PD patients undergoing STN-DBS. Clusters corresponding to maximum improvement in symptoms were in the posterior, superior and lateral portion of the STN. Greater connectivity to the primary motor area, supplementary motor area and prefrontal cortex was predictive of higher improvement in tremor, bradykinesia and rigidity, and rigidity respectively. The third experiment (chapter 5) examined pyramidal tract (PT) activation in 20 PD patients with STN-DBS. Volume of tissue activation (VTA) around DBS contacts were modelled in relation to the PT. VTA/ PT overlap predicted EMG activation thresholds. Sections II: Pilot data suggest that probabilistic tractography techniques can be used to segment the ventrolateral (VL) and ventroposterior (VP) thalamus based on cortical and cerebellar connectivity in nine patients who underwent thalamic DBS for tremor (chapter 6). The thalamic area, best representing the ventrointermedialis nucleus (VIM), was connected to the contralateral dentate cerebellar nucleus. Streamlines corresponding to the dentato-rubro-thalamic tract (DRT) connected M1 to the contralateral dentate nucleus via the dentato-thalamic area. Good response was seen when the active contact’s VTA was in the thalamic area with the highest connectivity to the contralateral dentate nucleus. Section III: The efficacy and safety of DBS in the ventral tegmental area (VTa) in the treatment of chronic cluster headache (CH) and short lasting unilateral neuralgiform headache attacks (SUNA) were examined (chapters 7 and 8). The optimum stimulation site within the VTa that best controls symptoms was explored (chapter 9). The average responders’ deep brain stimulation activation volume lay on the trigemino-hypothalamic tract, connecting the trigeminal system and other nociceptive brainstem nuclei, with the hypothalamus, and the prefrontal and mesial temporal areas

Proton Magnetic Resonance Spectroscopy of Intracranial Lesions: Assessment of differences between Tumours and Tumour like Lesions and Its applicability in Brain Lesion Characterization

Intracranial lesions are a significant health problem and present several imaging challenges. The role of imaging is no longer limited to merely providing anatomic details of the exact location of the pathology. Advanced Magnetic Resonance Imaging (MRI) techniques allow insight into the chemical makeup of certain compounds within these pathologic lesions. In vivo Proton MR Spectroscopy (1H MRS), a non-invasive technique which provides metabolic information can complement the anatomical changes found in radiological examinations of various intracranial lesions increasing diagnostic specificity. The present investigation was carried out a) To determine if there are specific MRS findings which could help differentiate between neoplastic and non –neoplastic lesions and also to identify the presence or absence of MRS features which could help differentiate one neoplasm from another. b)to determine if MRS findings could help grade gliomas pre operatively. c) To determine if MRS findings could help differentiate irradiated residual/recurrent tumours from radiation necrosis. d) To determine if MRS findings could help differentiate necrotic tumours from infective lesions such as abscesses. CONCLUSION: MR Spectroscopy in addition to appropriate conventional MRI sequences provides useful supplementary information and has a potential to validate treatment strategies. This could influence decision making with respect to prognosis and therapy in patients with intracranial lesions. Current Neuro - Imaging techniques enable use of multiple modalities to enhance the accuracy of non-invasive diagnosis. This study emphasizes the utility and validity of a simple add on technique of MRS over MRI to provide additional information in establishing the possible aetiological diagnosis of intracranial lesions. This study helps radiologists to improve diagnostic accuracy of MRI using the additional modality of MRS. MRS could help in clinical decision making in difficult cases e.g.in distinguishing neoplastic from non-neoplastic lesions. During the last few years there has been an exponential growth in MRS. The phenomenal advances in neuroimaging of the brain are resulting in a paradigm change in the clinician’s approach to diagnosing and managing intracranial conditions. Advances in the ultra precise delineation of anatomical changes in the brain have resulted in increasing precision in separating normal from abnormal brain tissue. However this has not kept pace with identifying the nature of the abnormal brain tissue. For several decades humankind has preferred non-invasive methods in establishing a definite pathological diagnosis. This is particularly true for cerebral lesions. This study appears to indicate, that one is now justified, in carrying out larger studies to confirm the present findings that MRS could be a valuable diagnostic tool in identifying certain types of cerebral pathology. CLINICAL APPLICATIONS & SUGGESTIONS: This study has enabled development of a few guidelines in the use of MR spectroscopy, as an add-on modality, to improve diagnostic accuracy, in certain categories of lesions i.e. neoplasm versus nonneoplasm, high grade tumours versus low grade tumours, high grade tumours versus metastases, recurrent tumours versus radiation necrosis, cystic non-tumoural lesions versus cystic tumours and improved follow up of polyphasic demyelinating conditions i.e. multiple sclerosis. 1. It is desirable that all patients with intra cranial space occupying lesions referred for MRI also undergo MRS, to provide additional information which may help differentiate a neoplasm from nonneoplasms. This could avoid surgical treatment in some instances. 2. MRS can be considered as a suitable, complementary modality to be used when a doubt exists in defining whether a tumour is low or high grade. 3. Solitary metastasis always is difficult to diagnose and may be confused with other high grade tumours. While it is challenging to use single voxel MRS technique to distinguish between the two, MV-MRS technique would be more useful to differentiate metastasis from high grade glioma. 4. In follow up of treated patients of brain tumour, especially after surgery, radiotherapy and/or chemotherapy, the differentiation between recurrent tumour and radiation necrosis can be difficult. Making this distinction is critical for treatment and MRS appears to be a useful tool to distinguish between the two. 5. In analyzing the use of MRS in tuberculous and pyogenic abscess, MRS was found to be useful in distinguishing tuberculous from pyogenic abscesses. 6. In polyphasic demyelinating conditions such as Multiple Sclerosis, MRS plays a valuable role not only in initial diagnosis but also in follow up. Degree of neuronal loss, a prognostic factor, can indirectly be titrated through MRS findings on follow up studies

The modulation effects of repeated transcutaneous auricular vagus nerve stimulation on the functional connectivity of key brainstem regions along the vagus nerve pathway in migraine patients

BackgroundPrevious studies have shown a significant response to acute transcutaneous vagus nerve stimulation (taVNS) in regions of the vagus nerve pathway, including the nucleus tractus solitarius (NTS), raphe nucleus (RN) and locus coeruleus (LC) in both healthy human participants and migraine patients. This study aims to investigate the modulation effect of repeated taVNS on these brainstem regions by applying seed-based resting-state functional connectivity (rsFC) analysis.Methods70 patients with migraine were recruited and randomized to receive real or sham taVNS treatments for 4 weeks. fMRI data were collected from each participant before and after 4 weeks of treatment. The rsFC analyses were performed using NTS, RN and LC as the seeds.Results59 patients (real group: n = 33; sham group: n = 29) completed two fMRI scan sessions. Compared to sham taVNS, real taVNS was associated with a significant reduction in the number of migraine attack days (p = 0.024) and headache pain intensity (p = 0.008). The rsFC analysis showed repeated taVNS modulated the functional connectivity between the brain stem regions of the vagus nerve pathway and brain regions associated with the limbic system (bilateral hippocampus), pain processing and modulation (bilateral postcentral gyrus, thalamus, and mPFC), and basal ganglia (putamen/caudate). In addition, the rsFC change between the RN and putamen was significantly associated with the reduction in the number of migraine days.ConclusionOur findings suggest that taVNS can significantly modulate the vagus nerve central pathway, which may contribute to the potential treatment effects of taVNS for migraine.Clinical Trial Registration: http://www.chictr.org.cn/hvshowproject.aspx?id=11101, identifier ChiCTR-INR-17010559

Neuroimaging - Clinical Applications

Modern neuroimaging tools allow unprecedented opportunities for understanding brain neuroanatomy and function in health and disease. Each available technique carries with it a particular balance of strengths and limitations, such that converging evidence based on multiple methods provides the most powerful approach for advancing our knowledge in the fields of clinical and cognitive neuroscience. The scope of this book is not to provide a comprehensive overview of methods and their clinical applications but to provide a "snapshot" of current approaches using well established and newly emerging techniques