Hippocampal Neurometabolite Changes in Hypothyroidism: An In Vivo (1) H Magnetic Resonance Spectroscopy Study Before and After Thyroxine Treatment.

The hippocampus is a thyroid hormone receptor-rich region of the brain. A change in thyroid hormone levels may be responsible for an alteration in hippocampal-associated function, such as learning, memory and attention. Neuroimaging studies have shown functional and structural changes in the hippocampus as a result of hypothyroidism. However, the underlying process responsible for this dysfunction remains unclear. Therefore, the present study aimed to investigate the metabolic changes in the brain of adult hypothyroid patients during pre- and post-thyroxine treatment using in vivo proton magnetic resonance spectroscopy ((1) H MRS). (1) H MRS was performed in both healthy control subjects (n = 15) and hypothyroid patients (n = 15) (before and after thyroxine treatment). The relative ratios of the neurometabolites were calculated using the linear combination model (LCModel). Our results revealed a significant decrease of glutamate (Glu) (P = 0.045) and myo-inositol (mI) (P = 0.002) levels in the hippocampus of hypothyroid patients compared to controls. No significant changes in metabolite ratios were observed in the hypothyroid patients after thyroxine treatment. The findings of the present study reveal decreased Glu/tCr and mI/tCr ratios in the hippocampus of hypothyroid patients and these metabolite alterations persisted even after the patients became clinically euthyroid subsequent to thyroxine treatment.

Alterations of Functional Connectivity Among Resting-State Networks in Hypothyroidism.

Hypothyroidism affects brain functioning as suggested by various neuroimaging studies. The primary focus of the present study was to examine whether hypothyroidism would impact connectivity among resting-state networks (RSNs) using resting-state functional magnetic resonance imaging (rsfMRI). Twenty-two patients with hypothyroidism and 22 healthy controls were recruited and scanned using rsfMRI. The data were analysed using independent component analysis and a dual regression approach that was applied on five RSNs that were identified using fsl software (http://fsl.fmrib.ox.ac.uk). Hypothyroid patients showed significantly decreased functional connectivity in the regions of the right frontoparietal network (frontal pole), the medial visual network (lateral occipital gyrus, precuneus cortex and cuneus) and the motor network (precentral gyrus, postcentral gyrus, precuneus cortex, paracingulate gyrus, cingulate gyrus and supramarginal gyrus) compared to healthy controls. The reduced functional connectivity in the right frontoparietal network, the medial visual network and the motor network suggests neurocognitive alterations in hypothyroid patients in the corresponding functions. However, the study would be further continued to investigate the effects of thyroxine treatment and correlation with neurocognitive scores. The findings of the present study provide further interesting insights into our understanding of the action of thyroid hormone on the adult human brain.

Investigation of prolonged hypobaric hypoxia-induced change in rat brain using T2 relaxometry and diffusion tensor imaging at 7T.

The present study examines the change in water diffusion properties of the corpus callosum (CC) and the hippocampus, in response to prolonged hypobaric hypoxia (HH) stress, using in vivo magnetic resonance imaging (MRI) modalities such as T2 relaxometry and diffusion tensor imaging (DTI). Three groups of rats (n=7/group) were exposed to a simulated altitude of 6700m above sea level for the duration of 7, 14 and 21days, respectively. Data were acquired pre-exposure, post-exposure and after 1week of normoxic follow-up in each group. The increment in T2 values with no apparent diffusion coefficient (ADC) change in the CC after 7 and 14days of HH exposure indicated mixed (vasogenic and cytotoxic) edema formation. After 1week of normoxia, 7-day HH-exposed rats showed a decrease in ADC values in the CC, probably due to cytotoxic edema. A delayed decrease in ADC values was observed in the hippocampus after 1week normoxic follow-up in 7- and 14-day HH groups giving an insight of cytotoxic edema formation. Interestingly, 21-day HH-exposed rats did not show change in ADC values. The decrease in T2 values after 14 and 21days in the hippocampal region depicts iron deposition, which was confirmed by histopathology. This study successfully demonstrated the use of MRI modality to trace water diffusion changes in the brain due to prolonged HH exposure.

Diffusion tensor tractography in hypothyroidism and its correlation with memory function.

Diffusion tensor tractography (DTT) was performed to determine the microstructural changes in the white matter fibre tracts of hypothyroid patients compared to controls and to correlate these changes with memory dysfunction scores. DTT and Postgraduate Institute Memory Scale test were performed in eight hypothyroid patients and eight healthy controls. Diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and mean diffusivity (MD)] from all of the major cerebral tracts were calculated and a comparison was made between the patient group and controls. Pearson's correlation was performed between Memory Dysfunction score and DTI measures. Significant changes in DTI measures were observed in various white matter fibre tracts in hypothyroid patients compared to controls. In hypothyroid patients, an inverse correlation of Memory Dysfunction score with FA was observed in the right and left inferior fronto-occipital fasciculus, whereas a positive correlation with MD was observed in the right anterior thalamic radiation among all white matter tracts. These findings suggest that microstructural changes in white matter fibres may contribute to the underlying dysfunction in memory in hypothyroid patients.

Demyelinating evidences in CMS rat model of depression: a DTI study at 7 T.

Depression is among the most debilitating diseases worldwide. Long-term exposure to stressors plays a major role in development of human depression. Chronic mild stress (CMS) seems to be a valid animal model for depression. Diffusion tensor imaging (DTI) is capable of inferring microstructural abnormalities of the white matter and has shown to serve as non-invasive marker of specific pathology. We developed a CMS rat model of depression and validated with behavioral experiments. We measured the diffusion indices (mean diffusivity (MD), fractional anisotropy (FA), axial (λ∥) and radial (λ⊥) diffusivity) to investigate the changes in CMS rat brain during depression onset. Diffusion indices have shown to be useful to discriminate myelin damage from axon loss. DTI was performed in both control and CMS rats (n=10, in each group) and maps of FA, MD, λ∥ and λ⊥ diffusivity values were generated using in-house built software. The diffusion indices were calculated by region of interest (ROI) analysis in different brain regions like the frontal cortex, hippocampus, hypothalamus, cingulum, thalamus, caudate putamen, corpus callosum, cerebral peduncle and sensory motor cortex. The results showed signs of demyelination, reflected by increased MD, decreased FA and increased λ⊥. The results also suggest a possible role of edema or inflammation concerning the brain morphology in CMS rats. The overall finding using DTI suggests there might be a major role of loss of myelin sheath, which leads to disrupted connectivity between the limbic area and the prefrontal cortex during the onset of depression. Our findings indicate that interpretation of these indices may provide crucial information about the type and severity of mood disorders.

Assessment of lexical semantic judgment abilities in alcohol-dependent subjects: an fMRI study.

Neuropsychological studies have shown that alcohol dependence is associated with neurocognitive deficits in tasks requiring memory, perceptual motor skills, abstraction and problem solving, whereas language skills are relatively spared in alcoholics despite structural abnormalities in the language-related brain regions. To investigate the preserved mechanisms of language processing in alcohol-dependents, functional brain imaging was undertaken in healthy controls (n=18) and alcohol-dependents (n=16) while completing a lexical semantic judgment task in a 3 T MR scanner. Behavioural data indicated that alcohol-dependents took more time than controls for performing the task but there was no significant difference in their response accuracy. fMRI data analysis revealed that while performing the task, the alcoholics showed enhanced activations in left supramarginal gyrus, precuneus bilaterally, left angular gyrus, and left middle temporal gyrus as compared to control subjects. The extensive activations observed in alcoholics as compared to controls suggest that alcoholics recruit additional brain areas to meet the behavioural demands for equivalent task performance. The results are consistent with previous fMRI studies suggesting compensatory mechanisms for the execution of task for showing an equivalent performance or decreased neural efficiency of relevant brain networks. However, on direct comparison of the two groups, the results did not survive correction for multiple comparisons; therefore, the present findings need further exploration.

Voxel-based morphometric analysis in hypothyroidism using diffeomorphic anatomic registration via an exponentiated lie algebra algorithm approach.

The present study aimed to investigate whether brain morphological differences exist between adult hypothyroid subjects and age-matched controls using voxel-based morphometry (VBM) with diffeomorphic anatomic registration via an exponentiated lie algebra algorithm (DARTEL) approach. High-resolution structural magnetic resonance images were taken in ten healthy controls and ten hypothyroid subjects. The analysis was conducted using statistical parametric mapping. The VBM study revealed a reduction in grey matter volume in the left postcentral gyrus and cerebellum of hypothyroid subjects compared to controls. A significant reduction in white matter volume was also found in the cerebellum, right inferior and middle frontal gyrus, right precentral gyrus, right inferior occipital gyrus and right temporal gyrus of hypothyroid patients compared to healthy controls. Moreover, no meaningful cluster for greater grey or white matter volume was obtained in hypothyroid subjects compared to controls. Our study is the first VBM study of hypothyroidism in an adult population and suggests that, compared to controls, this disorder is associated with differences in brain morphology in areas corresponding to known functional deficits in attention, language, motor speed, visuospatial processing and memory in hypothyroidism.

Phosphorous magnetic resonance spectroscopy-based skeletal muscle bioenergetic studies in subclinical hypothyroidism.

BACKGROUND: Subclinical hypothyroidism (sHT) is considered to be a milder form of thyroid dysfunction. Few earlier studies have reported neuromuscular symptoms as well as impaired muscle metabolism in sHT patients. AIM/OBJECTIVE: In this study we report our findings on muscle bioenergetics in sHT patients using phosphorous magnetic resonance spectroscopy (31P MRS) and look upon the possibility to use 31P MRS technique as a clinical marker for monitoring muscle function in subclinical thyroid dysfunction. SUBJECTS AND METHODS: Seventeen normal subjects, 15 patients with sHT, and 9 patients with hypothyroidism performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MR Spectroscopy measurements of inorganic phosphate (Pi), phosphocreatine (PCr), and ATP of the calf muscle were taken during rest, at the end of exercise and in the recovery phase. PCr recovery rate constant (kPCr) and oxidative capacity were calculated by monoexponential fit of PCr vs time (t) at the beginning of recovery. RESULTS: We observed that changes in some of the phosphometabolites (increased phosphodiester levels and Pi concentration) in sHT patients which were similar to those detected in patients with hypothyroidism. However, our results do not demonstrate impaired muscle oxidative metabolism in sHT patients based upon PCr dynamics as observed in hypothyroid patients. CONCLUSIONS: 31P MRS-based PCr recovery rate could be used as a marker for monitoring muscle oxidative metabolism in sub clinical thyroid dysfunction.

Cortical activation during finger tapping in thyroid dysfunction: a functional magnetic resonance imaging study.

Thyroid dysfunction is associated with attention deficit and impairment of the motor system (muscle weakness and fatigue). This paper investigates possible motor function deficit in thyroid patients,compared to the controls. Functional MRI studies (fMRI)were carried out in five hypo and five hyperthyroid patients and six healthy volunteers. Whole brain imaging was performed using echo planar imaging (EPI)technique, on a 1.5T whole body MR system (Siemens Magnetom Vision). The task paradigm consisted of 8 cycles of active and reference phases of 6 measurements each, with right index finger tapping at a rate of 120 taps/min. Post-processing was performed using statistical parametric mapping on a voxel-by-voxel basis using SPM99. Clusters of activation were found in the contralateral hemisphere in primary somatomotor area (M1), supplementary motor area (SMA), somatosensory,auditory receptive and integration areas, inferior temporal lobe, thalamus and cerebellum. Increased clusters of activation were observed in M1 in thyroid subjects as compared to controls and with bilateral activation of the primary motor cortex in two hyperthyroid patients. The results are explained in terms of increased functional demands in thyroid patients compared to volunteers for the execution of the same task.

Role of in vivo proton MR spectroscopy in the evaluation of adult brain lesions: our preliminary experience.

CONTEXT: A definite diagnosis and characterization of intracranial mass lesions, based on structural Magnetic Resonance Imaging (MRI) alone may be difficult. In such cases Proton Magnetic Resonance Spectroscopy (1H-MRS) along with other non-invasive techniques represents an advance in the specificity of brain lesion diagnosis. AIMS: The primary aim of this study was to evaluate the extent of the utility of 1H-MRS in adult brain tumors and their differentiation from similar-appearing space-occupying lesions. MATERIAL AND METHODS: MRS studies were performed on 1.5 Tesla whole body MR system using standard imaging head coil. Sixty patients (aged 30-65 years), including 35 males (31-65 years) and 25 females (30-65 years) were studied, along with 25 age-matched healthy volunteers (30-64 years). The Student 't' test was used to statistically analyze the spectroscopic data for significant difference in the metabolite ratios of the lesions from normal brain tissue. RESULTS: The Cho/Cr ratio was significantly raised in low and high-grade glioma and meningioma patients (1.85 +/- 0.36, 3.50 +/- 1.00 and 6.65 +/- 2.83 respectively) (mean +/- standard deviation), as compared with the control group (1.16 +/- 0.18); and NAA/Cr and NAA/Cho ratios were found to be lower than normal values in our study (P<0.01). However, in the non-neoplastic lesions, the Cho/Cr ratios were not statistically significant. The tubercular lesions revealed an average Cho/Cr ratio of 1.24 +/- 0.18, while it was 1.14 +/- 0.07 for infarcts. CONCLUSION: MR Spectroscopy was useful to arrive at a more definitive diagnosis in doubtful intracranial space-occupying lesions with similar morphological imaging patterns.

Functional magnetic resonance imaging of the primary motor cortex in humans: response to increased functional demands.

Functional magnetic resonance imaging (fMRI) studies have been performed on 20 right handed volunteers at 1.5 Tesla using echo planar imaging (EPI) protocol. Index finger tapping invoked localized activation in the primary motor area. Consistent and highly reproducible activation in the primary motor area was observed in six different sessions of a volunteer over a period of one month. Increased tapping rate resulted in increase in the blood oxygenation level dependent (BOLD) signal intensity as well as the volume/area of activation (pixels) in the contralateral primary motor area up to tapping rate of 120 taps/min (2 Hz), beyond which it saturates. Activation in supplementary motor area was also observed. The obtained results are correlated to increased functional demands.

Co-existence of dual intracranial pathology clinical relevance of proton MRS.

The co-existence of neuro-cysticercosis (NCC) and intracranial neoplasm in an individual is a rare entity. Atypical presentation of cerebral cysticercosis may mimic glioma, metastasis, cerebral abscess or vice versa. The dual existence of these two lesions have led to several postulates which may have clinical impact in due course of time i.e. NCC as an oncogenetic factor for glioma or similarity of antigen found in glioma and NCC etc. An adequate management of such cases poses a challenge to both imageologists as well as clinicians. Thus, a proper diagnostic evaluation is essential for successful management of such cases. MR spectroscopy (MRS), although still a clinical research tool, may be extremely useful for exclusion or confirmation of neoplastic lesions in such a clinical scenario. The findings of MRS in collaboration with imaging parameters may increase the diagnostic yield of a MR investigation. The authors encountered five cases of dual intracranial pathologies i.e. neurocysticercosis and glioma. MR spectroscopy was useful to arrive at a definitive diagnosis in such a situation.

Frontal lobe proton magnetic-resonance spectroscopy in Graves' disease: a pilot study.

Patients with hyperthyroidism may show impaired performance on several neuropsychological tests that require complex visual discrimination, conceptualization, mental flexibility or organization. These neurocognitive impairments appear to be consistent with prefrontal lobe dysfunction. This pilot study was undertaken to characterize the metabolite profile in the right prefrontal cortex in six patients with untreated Graves' disease by using in vivo proton magnetic-resonance spectroscopy (1H-MRS). For comparison, 1H-MRS was also carried out in seven healthy controls. The choline/creatine (Cho/Cr) and N-acetyl aspartate/creatine (Naa/Cr) ratios were determined. Cho/Cr ratios of the hyperthyroid patients were significantly lower than that of controls (means +/- SD = 0.61 +/- 0.09 vs. 0.90 +/- 0.18, p = .05). The two groups did not differ in their Naa/Cr ratios. Follow-up data after antithyroid treatment were available in three patients: Cho/Cr ratios were higher after treatment (euthyroidism) than before treatment (1.06 vs. 0.55; 0.82 vs. 0.54; 1.15 vs. 0.76). Tentatively, these preliminary data are most consistent with reversible reductions in the concentrations of choline-containing compounds (especially glycerophosphocholine and phosphocholine) in the prefrontal area during hyperthyroidism. However, these findings await confirmation by a definitive study with a larger sample size. A possible explanation of the findings is an altered brain cholinergic-adrenergic balance in hyperthyroidism.

Effects of radiation therapy on the human normal brain (white matter) visualized by MR imaging.

Sequential MR imaging could provide information related to the pathological changes due to the application of external cytotoxic agents such as radiotherapy on the central nervous system. This paper describes the results of our attempt to demonstrate short-term changes associated with normal brain during and immediately following radiotherapy when the whole brain is irradiated for malignant conditions. No observable changes were found in the normal brain parenchyma in any of the patients (n = 8) in T1-, T2-, and proton-density-weighted images in the sequential scans in the first and second weeks and immediately following radiotherapy. Also, no changes were observed in the normal brain appearance at 2 mo (n = 6), up to 6 mo (n = 1), and up to 15 mo (n = 1) after completion of radiotherapy.

Magnetic resonance evaluation of spinal dysraphism in children.

Magnetic resonance (MR) imaging of the spine was performed as the initial imaging technique in 20 children when spinal dysraphism was suspected clinically and plain radiographs showed spina bifida. The correlation with surgical findings indicated that MR provided accurate information preoperatively in all the cases. Some unusual observations in cases with spina bifida cystica and occulta are discussed. It is concluded that plain radiograph and MR complete the preoperative radiologic evaluation of cases with spinal dysraphism.

magnetic resonance diagnosis of spinal arachnoid cyst. A report of two cases.

Magnetic resonance (MR) findings in one case each of extradural and intradural arachnoid cyst are described. Thoracic segments were involved in both cases. The cysts were slightly more intense than cerebrospinal fluid in both cases on T1 weighted images. The nature and extent of the lesions were better demonstrated on MR images as compared with combined myelography and computed tomography.

Magnetic resonance in obstructive jaundice.

Twelve cases of obstructive jaundice in whom ultrasound failed to demonstrate the site and/or the cause of obstruction of the biliary tract were examined with magnetic resonance imaging (MRI), correctly diagnosing the site and cause of obstruction in 10 of 12 surgically proven cases. In one case of cholangiocarcinoma, the site of obstruction was well shown on MR but a definite cause could not be ascertained. In another patient who developed intermittent jaundice following surgery for choledochal cyst, MR demonstrated a solitary stone in the common hepatic duct. Surgical confirmation could not be achieved as the patient was lost to follow up. There were 6 cases of choledocholithiasis, 3 cases of gall bladder carcinoma and one case each of pancreatic adenocarcinoma and cholangiocarcinoma. It is believed that MRI will provide obstructive jaundice and will be able to minimize the use of percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP) in view of its ability to perform multiplanar imaging in multiple sequences.

Cysticercosis of the brain shown by magnetic resonance imaging.

Fifteen patients in whom the diagnosis of cysticercosis of the brain was suggested by computed tomography (CT) were further studied with magnetic resonance imaging (MRI). Besides lesions in the substance of the hemispheres, cysts were found adjacent to and within the ventricles, the brainstem, cerebellum and subarachnoid space. Magnetic resonance imaging showed brain involvement out of proportion to what was shown by CT. The eccentrically placed mural nodule within a cyst, the pathognomonic lesion of cysticercosis, was seen in all cases with MRI. The various stages of development of the cysticercus larva were seen in one individual. An attempt is made to illustrate the various stages of development by means of MR images, and a possible pathological explanation is offered. The authors believe that MRI provides diagnostic information in this disease and dispenses with the need for enhanced CT examination.

MR imaging of intracranial tuberculomas.

Eight patients with intracranial tuberculomas were studied with CT and magnetic resonance (MR) imaging. Large, ring enhancing, solid lesions on CT showed low intensity on T2-weighted images and intermediate intensity on T1-weighted images. Small lesions, with ring enhancement on CT, showed central bright signal on T2-weighted images with a peripheral low intensity rim surrounded by high intensity edema. The MR imaging features of the tuberculomas were found to be distinct from those of abscesses, metastases, and gliomas.