Serial MRI Scans Research Articles

Pornography addiction: A neuroscience perspective

A significant postulate of this commentary is that all addictions create, in addition to chemical changes in the brain, anatomical and pathological changes which result in various manifestations of cerebral dysfunction collectively labeled hypofrontal syndromes. In these syndromes, the underlying defect, reduced to its simplest description, is damage to the “braking system” of the brain. They are well known to clinical neuroscientists, especially neurologists and neurosurgeons, for they are also seen with tumors, strokes, and trauma. Indeed, anatomically, loss of these frontal control systems is most apparent following trauma, exemplified by progressive atrophy of the frontal lobes seen in serial MRI scans over time.

Radical Resection of Adult Low Grade Oligodendroglioma without Adjuvant Therapy: Results of a Prospective Treatment Protocol—Surgical Treatment of Low-Grade Oligodendroglioma

The goal of this work was to demonstrate prospectively that maximal surgical resection of low grade oligodendrogliomas without adjuvant therapy does not reduce life expectancy over that of historical controls. All patients with surgically accessible grade II oligodendrogliomas underwent maximal resection using stereotactic guidance and/or cortical mapping and were followed with serial MRI scans without adjuvant therapy until either progression or spread into brain regions deemed not surgically resectable. Nineteen patients were treated between 1993 and 2006. Ten patients required reoperation an average of 55 months after their first surgery. Nine patients progressed to anaplastic tumors an average of 42 months after their first surgery: six patients died from their tumors an average of 73 months after diagnosis, two are still alive 76 and 18 months after progression, and one was lost to follow up. Ten patients are alive and progression-free an average of 116 months after diagnosis, one of whom was lost to follow up at 106 months from diagnosis. Four patients are alive and event-free an average of 125 months after diagnosis. All are male and three had tumors in the superior frontal gyrus. The event-free survival, progression-free survival, and overall survival of our patients are not worse than those of patients treated with postoperative adjuvant therapy. Withholding adjuvant therapy at diagnosis appears to be safe. It will be important to establish the molecular differences between the patients who did very well and those who progressed so that adjuvant therapy could be offered to the latter.

Should Gamma Knife be Offered as a Primary Treatment for a Resectable Glomus Jugulare Tumor?

ABSTRACTAttempted total resections is the preferred treatment option in the management of glomus jugulare tumors in most subjects. In the elderly patients, it may be advisable to leave a tiny residue over the involved cranial nerve to preserve function. In a medically unfit and anesthetically high-risk subject observation with serial MRI scans is the preferred line of management. If in such a patient there occurs brainstem compression, it is prudent to only operate the intracranial part to relieve the compression explaining the very high-risk in this group. Radiotherapy is not to be offered as a primary treatment for glomus jugulare tumors.

Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

BackgroundAn increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.ObjectiveTo determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159).Methods and FindingsSingle-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans.ResultsA total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category.Conclusions and SignificanceThe accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease.Trial RegistrationControlled-Trials.com ISRCTN94410159

B15 Rat bone marrow derived mesenchymal stem cells post differentiation to neurotrophic factor secreting cells migrate towards quinolinic acid lesion

BackgroundQuinolinic acid (QA) induced striatal lesion is a well established model for excitotoxicity, one of the key hallmarks of Huntington's disease pathophysiological processes. Stem cell based treatment is a promising...

Combining Cortical Thickness Analysis and Clinical Measures to Predict Alzheimer's Disease

clinical and research reasons. Identifying these subjects as soon as possible is crucial, first for the patient benefit and second for speeding up and track the effect of different therapeutical interventions. We hypothesise that the prediction will be facilitated by structural MRI investigating whole brain atrophy, as well as regional alterations in cortical features (grey matter volume, thickness, and surface area) by using serial MRI scans, with a three months follow up period. Methods: This study focused on the MCI group (N 1⁄4 92), out of which 23 were diagnosed with AD 12 months from the baseline clinical assessment. Whole brain atrophy was assessed by iterative principal component analysis (IPCA). The Fischl and Dale pipeline provided measures of regional brain atrophy and cortical thickness. The structural MRI data collected at baseline and at 3 months were analysed cross-sectionally and longitudinally using multivariate statistical models. Results: Preliminary analyses point out that whole-brain measurements are not robust predictors of conversion to AD. Conclusions: This is the first study exploring structural MRI data with only 3 months follow-up period. Although a 3 months follow up period may seem too short given the complexity of neurodegenerative processes leading to overt brain atrophy, we are currently only exploring the potential information provided by the wealth of data produced by complex image analysis procedures.

Evolution of gray matter atrophy on serial MRI scans predicting the progression from MCI to Alzheimer's

Evolution of gray matter atrophy on serial MRI scans predicting the progression from MCI to Alzheimer's

Articular Cartilage Regeneration with Autologous Peripheral Blood Stem Cells and Hyaluronic Acid (SS-34)

Articular Cartilage Regeneration with Autologous Peripheral Blood Stem Cells and Hyaluronic Acid (SS-34)

Subregional neuroanatomical change as a biomarker for Alzheimer's disease.

Regions of the temporal and parietal lobes are particularly damaged in Alzheimer's disease (AD), and this leads to a predictable pattern of brain atrophy. In vivo quantification of subregional atrophy, such as changes in cortical thickness or structure volume, could lead to improved diagnosis and better assessment of the neuroprotective effects of a therapy. Toward this end, we have developed a fast and robust method for accurately quantifying cerebral structural changes in several cortical and subcortical regions using serial MRI scans. In 169 healthy controls, 299 subjects with mild cognitive impairment (MCI), and 129 subjects with AD, we measured rates of subregional cerebral volume change for each cohort and performed power calculations to identify regions that would provide the most sensitive outcome measures in clinical trials of disease-modifying agents. Consistent with regional specificity of AD, temporal-lobe cortical regions showed the greatest disease-related changes and significantly outperformed any of the clinical or cognitive measures examined for both AD and MCI. Global measures of change in brain structure, including whole-brain and ventricular volumes, were also elevated in AD and MCI, but were less salient when compared to changes in normal subjects. Therefore, these biomarkers are less powerful for quantifying disease-modifying effects of compounds that target AD pathology. The findings indicate that regional temporal lobe cortical changes would have great utility as outcome measures in clinical trials and may also have utility in clinical practice for aiding early diagnosis of neurodegenerative disease.

Improvement in Presenting Visual Deficits and Diplopia in Patients with Orbital Nerve Sheath and Orbital Apex Meningiomas Treated with Fractionated Stereotactic Radiotherapy

Improvement in Presenting Visual Deficits and Diplopia in Patients with Orbital Nerve Sheath and Orbital Apex Meningiomas Treated with Fractionated Stereotactic Radiotherapy

Baseline CSF p-tau levels independently predict progression of hippocampal atrophy in Alzheimer disease

To investigate whether baseline CSF biomarkers are associated with hippocampal atrophy rate as a measure of disease progression in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and controls, controlling for baseline neuropsychological and MRI findings. We assessed data from 31 patients with AD, 25 patients with MCI, and 19 controls (mean age 68 +/- 8 years; 39 [52%] female) who visited our memory clinic and had received serial MRI scanning (scan interval 1.7 +/- 0.7 years). At baseline, CSF biomarkers (amyloid beta 1-42, tau, and tau phosphorylated at threonine 181 [p-tau]) were obtained, as well as neuropsychological data. Baseline MRI scans were assessed using visual rating scales for medial temporal lobe atrophy (MTA), global cortical atrophy, and white matter hyperintensities. Hippocampal atrophy rates were estimated using regional nonlinear "fluid" registration of follow-up scan to baseline scan. Stepwise multiple linear regression, adjusted for age and sex, showed that increased CSF p-tau levels (beta [standard error]: -0.79 [0.35]) at baseline was independently associated with higher subsequent hippocampal atrophy rates (p < 0.05), together with poorer memory performance (0.09 [0.04]) and more severe MTA (-0.60 [0.21]). The association of memory function with hippocampal atrophy rate was explained by the link with diagnosis, because it disappeared from the model after we additionally corrected for diagnosis. Baseline CSF levels of tau phosphorylated at threonine 181 are independently associated with subsequent disease progression, as reflected by hippocampal atrophy rate. This effect is independent of baseline neuropsychological and MRI predictors. Our results imply that predicting disease progression can best be achieved by combining information from different modalities.

Non‐paraneoplastic limbic encephalitis associated with antibodies to potassium channels leading to bilateral hippocampal sclerosis in a pre‐pubertal girl

Limbic encephalitis (LE) is increasingly recognized as a precipitating factor of adult onset temporal lobe epilepsy frequently associated with bilateral hippocampal damage. So far, clinical data in children are rare and only comprise paraneoplastic forms of LE. We describe a 13-year-old pre-pubertal girl in whom non-paraneoplastic LE was diagnosed according to diagnostic criteria proposed by Bien and Elger (2007). The girl presented with a subacute syndrome comprising memory impairment, affective disturbances, and refractory temporal lobe seizures. Serial MRI scans demonstrated an initial temporo-medial swelling with T2/FLAIR signal increase progressing to bilateral hippocampal atrophy within seven months. Two years after onset of symptoms, antibodies to potassium channels were found to be slightly elevated. Immunosuppressive therapy with steroid-pulses was followed by a transient reduction of seizure frequency, even though this was started more than two years after onset of first symptoms. However, extended immunotherapy was refused by the patient's parents, so no full assessment of the treatment response was possible. In conclusion, this case shows that non-paraneoplastic LE leading to mesial temporal lobe epilepsy is not restricted to adult patients. The proposed diagnostic criteria therefore should be adapted for paediatric patients. Patients may profit from immunosuppressive therapy even when it is started at a late stage with already overt hippocampal sclerosis.

Alzheimer's Disease Neuroimaging Initiative: A one-year follow up study using tensor-based morphometry correlating degenerative rates, biomarkers and cognition

Tensor-based morphometry can recover three-dimensional longitudinal brain changes over time by nonlinearly registering baseline to follow-up MRI scans of the same subject. Here, we compared the anatomical distribution of longitudinal brain structural changes, over 12 months, using a subset of the ADNI dataset consisting of 20 patients with Alzheimer's disease (AD), 40 healthy elderly controls, and 40 individuals with mild cognitive impairment (MCI). Each individual longitudinal change map (Jacobian map) was created using an unbiased registration technique, and spatially normalized to a geometrically-centered average image based on healthy controls. Voxelwise statistical analyses revealed regional differences in atrophy rates, and these differences were correlated with clinical measures and biomarkers. Consistent with prior studies, we detected widespread cerebral atrophy in AD, and a more restricted atrophic pattern in MCI. In MCI, temporal lobe atrophy rates were correlated with changes in mini-mental state exam (MMSE) scores, clinical dementia rating (CDR), and logical/verbal learning memory scores. In AD, temporal atrophy rates were correlated with several biomarker indices, including a higher CSF level of p-tau protein, and a greater CSF tau/beta amyloid 1-42 (ABeta42) ratio. Temporal lobe atrophy was significantly faster in MCI subjects who converted to AD than in non-converters. Serial MRI scans can therefore be analyzed with nonlinear image registration to relate ongoing neurodegeneration to a variety of pathological biomarkers, cognitive changes, and conversion from MCI to AD, tracking disease progression in 3-dimensional detail.

Cortical volumes and atrophy rates in FTD-3 CHMP2B mutation carriers and related non-carriers

Frontotemporal dementia constitutes the third most prevalent neurodegenerative disease with dementia. We compared cortical structural changes in nine presymptomatic CHMP2B frontotemporal dementia mutation positive individuals with seven mutation negative family members. Using serial MRI scans with a mean interval of 16 months and surface based cortical segmentation we measured cortical thickness and volume, and quantified atrophy rates. Cortical thickness and atrophy rates were averaged within major lobes and focal effects were determined by parametric statistical maps.The volumetric atrophy rates in the presymptomatic CHMP2B mutation carriers were statistically significant, though of a lower magnitude than those previously reported in patients of other types of frontotemporal dementia. Cortical thickness measurements revealed cortical thinning in mutation carriers bilaterally in the frontal and occipital lobes, and in the left temporal lobe. Results indicated that cortical thickness has a higher sensitivity for detecting small changes than whole-brain volumetric measures. Comparing mutation carriers with non-carriers revealed increased atrophy rates in mutation carriers bilaterally in the inferio-temporal cortex, the superior frontal cortex, and the insular cortex. These findings indicated impairment of regions involved in both behaviour and language. The symptoms previously reported in clinical CHMP2B frontotemporal dementia patients are associated with the anatomically affected regions here found in the presymptomatic mutation carriers.

Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial

Interferon beta-1a and glatiramer acetate are commonly prescribed for relapsing-remitting multiple sclerosis (RRMS), but no published randomised trials have directly compared these two drugs. Our aim in the REGARD (REbif vs Glatiramer Acetate in Relapsing MS Disease) study was to compare interferon beta-1a with glatiramer acetate in patients with RRMS. In this multicentre, randomised, comparative, parallel-group, open-label study, patients with RRMS diagnosed with the McDonald criteria who had had at least one relapse within the previous 12 months were randomised to receive 44 mug subcutaneous interferon beta-1a three times per week or 20 mg subcutaneous glatiramer acetate once per day for 96 weeks to assess the time to first relapse. A subpopulation of 460 patients (230 from each group) also had serial MRI scans to assess T2-weighted and gadolinium-enhancing lesion number and volume. Treatments were assigned by a computer-generated randomisation list that was stratified by centre. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00078338. Between February and December, 2004, 764 patients were randomly assigned: 386 to interferon beta-1a and 378 to glatiramer acetate. After 96 weeks, there was no significant difference between groups in time to first relapse (hazard ratio 0.94, 95% CI 0.74 to 1.21; p=0.64). Relapse rates were lower than expected: 258 patients (126 in the interferon beta-1a group and 132 in the glatiramer acetate group) had one or more relapses (the expected number was 460). For secondary outcomes, there were no significant differences for the number and change in volume of T2 active lesions or for the change in the volume of gadolinium-enhancing lesions, although patients treated with interferon beta-1a had significantly fewer gadolinium-enhancing lesions (0.24 vs 0.41 lesions per patient per scan, 95% CI -0.4 to 0.1; p=0.0002). Safety and tolerability profiles were consistent with the known profiles for both compounds. The overall number and severity of adverse events were similar between the treatments and were not an important cause for discontinuation of the trial during the 96 weeks. There was no significant difference between interferon beta-1a and glatiramer acetate in the primary outcome. The ability to predict clinical superiority on the basis of results from previous studies might be limited by a trial population with low disease activity, which is an important consideration for ongoing and future trials in patients with RRMS.

Longitudinal Magnetic Resonance Imaging Features of Glioblastoma Multiforme Treated With Radiotherapy With or Without Brachytherapy

To compare temporal patterns of recurrent contrast enhancement in patients with glioblastoma multiforme (GBM) treated with brachytherapy plus external beam radiotherapy (EBRT) vs. EBRT alone. We evaluated serial MRI scans for 15 patients who received brachytherapy followed by EBRT (6000 cGy) and 20 patients who received standard EBRT alone (5940-6000 cGy). Brachytherapy consisted of permanent, low-activity (125)I seeds placed around the resection cavity at the time of initial gross total resection. Contrast enhancement (linear, nodular, feathery, or solid), serial progression, and location of contrast enhancement were described. In the EBRT group, 14 patients demonstrated focal nodular contrast enhancement along the resection cavity within 4 months. The 6 remaining EBRT patients developed either transient linear enhancement or no abnormal enhancement. In the brachytherapy plus EBRT group, 7 patients initially developed linear rim enhancement within 4 months that progressed to feathery contrast enhancement over the course of 1 to 2 years. Histopathology confirmed radiation necrosis in all 7 patients. The remaining 8 brachytherapy patients eventually developed focal nodular contrast enhancement along the resection cavity and tumor recurrence. Our data suggest that longitudinal MRI features differ between GBM patients treated with EBRT vs. brachytherapy plus EBRT. In both groups, nodular enhancement adjacent to or remote from the resection cavity strongly suggested tumor recurrence. Feathery enhancement, which progressed from linear rim enhancement immediately adjacent to the cavity, seen only in brachytherapy patients, strongly indicated radiation necrosis.

Conservative management of vestibular schwannomas: third review of a 10‐year prospective study

Seventy-two patients with a unilateral vestibular schwannoma have been treated conservatively for a median of 121 months. They have been followed prospectively by serial clinical examination, MRI scans and audiometry. Twenty-five patients (35%, 95% CI: 24-47) failed conservative management and required active intervention during the study. No factors predictive of tumour growth or failure of conservative management could be identified. Seventy-five per cent of failures occurred in the first half of the 10-year study. The median growth rate for all tumours at 10 years was 1 mm/year (range -0.53-7.84). Cerebellopontine angle tumours grew faster (1.4 mm/year) than intracanalicular tumours (0 mm/year, P < 0.01); 92% had growth rates under 2 mm/year. Hearing deteriorated substantially even in tumours that did not grow, but did so faster in tumours that grew significantly (mean deterioration in pure tone average at 0.5, 1, 2 and 3 kHz was 36 dB; speech discrimination scores deteriorated by 40%). Patients who failed conservative management had clinical outcomes that were not different from those who underwent primary treatment without a period of conservative management.

Asymmetric and Symmetric Unbiased Image Registration: Statistical Assessment of Performance.

Measures of brain changes can be computed from sequential MRI scans, providing valuable information on disease progression for neuroscientific studies and clinical trials. Tensor-based morphometry (TBM) creates maps of these brain changes, visualizing the 3D profile and rates of tissue growth or atrophy. In this paper, we examine the power of different nonrigid registration models to detect changes in TBM, and their stability when no real changes are present. Specifically, we investigate an asymmetric version of a recently proposed unbiased registration method, using mutual information as the matching criterion. We compare matching functionals (sum of squared differences and mutual information), as well as large deformation registration schemes (viscous fluid registration versus symmetric and asymmetric unbiased registration) for detecting changes in serial MRI scans of 10 elderly normal subjects and 10 patients with Alzheimer's Disease scanned at 2-week and 1-year intervals. We demonstrated that the unbiased methods, both symmetric and asymmetric, have higher reproducibility. The unbiased methods were also less likely to detect changes in the absence of any real physiological change. Moreover, they measured biological deformations more accurately by penalizing bias in the corresponding statistical maps.

Early anisotropy changes in the corpus callosum of patients with optic neuritis

Optic neuritis (ON) and any other early manifestation of multiple sclerosis (MS) are referred to as clinically isolated syndrome (CIS) as long as MS is suspected. In this prospective study we aimed to determine whether diffusion tensor imaging (DTI) could quantify structural changes in patients with early MS. A total of 24 patients and 15 control subjects were prospectively followed by clinical examinations and MRI. the main inclusion criterion was presentation with ON. Patients underwent serial MRI scans: MRI1 (baseline, n=24), MRI2 (mean 6.6 months, n=24), MRI3 (mean 13.0 months, n=14), MRI4 (mean 39.4 months, n=5). Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were derived from DTI. Four regions of interest (ROIs) were defined in normal-appearing white matter (NAWM). In the temporal course FA decreased in the genu of the callosal body (GCC) from MRI1 to MRI4 (P=0.005) and in the splenium of the callosal body (SCC) (P=0.006). Patients already had lower FA values in the SCC (P<0.01) on MRI1 compared with the controls. Patients had lower FA values in the GCC (P<0.01) starting from MRI2. Patients with definite MS on follow-up (n=9) showed a correlation between FA in the SCC and time (r=-0.40, P=0.004), whereas patients without progression did not. Our findings suggest that the corpus callosum is an early site for development of anisotropy changes in MS patients with ON. There seems to be a primary FA decrease in all patients with ON that only deteriorates in the group developing definite MS.

Reperfusion Half-Life

We hypothesized that the probability of reperfusion can be modeled by an exponential decay (ie, half-life) function and that this reperfusion half-life is decreased by thrombolytic treatment. Serial perfusion MRI scans were evaluated for evidence of reperfusion in intravenous tissue plasminogen activator-treated (n=45) and untreated (n=103) patients. The cumulative probability of reperfusion for each group was fit with exponential decay functions. The resulting reperfusion half-life (ie, the time it takes half the sample to reperfuse) was calculated. In untreated patients, a monoexponential decay function fit the data well (R(2)=0.95) with a half-life of 29.1 hours. In tissue plasminogen activator-treated patients, the data were best fit with a biexponential decay function (R(2)=0.99) that had a fast and a slow component. The fast component is attributable to tissue plasminogen activator therapy and has a half-life of 0.71 hours, whereas the slow component was similar to that of the untreated group. Approximately 3.5 hours after the start of treatment, the effect of tissue plasminogen activator on the probability of reperfusion was negligible. The probability of reperfusion can be well described by the reperfusion half-life. Determination of the fast component reperfusion half-life may be an approach to compare the relative potency of different thrombolytic agents.