•Trichotillomania (TTM) neurochemistry is understudied, with no prior research using magnetic resonance spectroscopy (MRS).•This study examined associations of TTM diagnosis, severity, and behavioral ...treatment response with MRS neurometabolites glutamate (Glu) and γ-aminobutyric acid (GABA) in cortico-striato-thalamo-cortical (CSTC) structures•Higher pretreatment levels of Glu in pACC and thalamus were associated with more severe TTM symptoms, while higher GABA levels in pACC were associated with less severe symptoms•Levels of GABA in putamen rose notably after treatment•Higher pretreatment levels of Glu in multiple regions (caudate, putamen, globus pallidus, thalamus, and white matter) predicted greater post-treatment decrease in TTM symptoms, while worse response was predicted by higher GABA in caudate and lower GABA in globus pallidus.•Together, these results link TTM symptoms with higher excitatory metabolism in pACC and thalamus and link behavioral therapy-derived symptom alleviation with suppression of CSTC direct-pathway activity.
Trichotillomania (TTM) is a chronic and impairing psychiatric disorder with suspected dysfunctional cortico-striato-thalamo-cortical (CSTC) circuit activity reflecting excitatory/inhibitory signaling imbalance. TTM neurochemistry is understudied, with no prior research using magnetic resonance spectroscopy (MRS). This pilot investigation examined associations between TTM diagnosis, symptom severity, and response to behavioral treatment with MRS neurometabolites glutamate (Glu) and γ-aminobutyric acid (GABA) in CSTC structures.
Proton echo-planar spectroscopic imaging (PEPSI) MRS was acquired from bilateral pregenual anterior cingulate cortex (pACC), caudate, putamen, globus pallidus, thalamus, and proximal white matter in 10 unmedicated girls with TTM, ages 9-17 years, before and after treatment, and from 13 age- and sex-matched healthy controls.
Nine of 10 TTM patients were treatment responders. Pretreatment mean Glu and GABA did not differ significantly between participants and controls. Pretreatment TTM symptoms were correlated with Glu in (left + right) pACC (r = 0.88, p = 0.02) and thalamus (r = 0.82, p = 0.012), and were negatively correlated with pACC GABA (r = -0.84, p = 0.034). Mean GABA in putamen increased 69% (baseline to post-treatment) (p = 0.027). Higher pretreatment Glu in caudate, putamen, globus pallidus, and thalamus predicted greater symptom decreases with treatment (all r < -0.6, p < 0.05); higher caudate GABA predicted less treatment-related symptom decline (r = 0.86, p = 0.014).
Small sample, GABA quantified with spectral fitting rather than editing.
Consistent with other neuroimaging, MRS reveals discrete CSTC chemical changes with effective behavior therapy, and possibly with TTM etiology. TTM symptoms relate to excess excitatory versus inhibitory signaling in pACC and thalamus; symptom improvement may reflect reduced excitatory drive of the CSTC direct-pathway activity.
Background
Attention deficit‐hyperactivity disorder (ADHD) is common in fetal alcohol spectrum disorders (FASD) but also in patients without prenatal alcohol exposure (PAE). Many patients diagnosed ...with idiopathic ADHD may actually have ADHD and covert PAE, a treatment‐relevant distinction.
Methods
We compared proton magnetic resonance spectroscopic imaging (MRSI; N = 44) and diffusion tensor imaging (DTI; N = 46) of the anterior corona radiata (ACR)—a key fiber tract in models of ADHD—at 1.5 T in children with ADHD with PAE (ADHD+PAE), children with ADHD without PAE (ADHD−PAE), children without ADHD with PAE (non‐ADHD+PAE), and children with neither ADHD nor PAE (non‐ADHD−PAE, i.e., typically developing controls). Levels of choline‐compounds (Cho) were the main MRSI endpoint, given interest in dietary choline for FASD; the main DTI endpoint was fractional anisotropy (FA), as ACR FA may reflect ADHD‐relevant executive control functions.
Results
For ACR Cho, there was an ADHD‐by‐PAE interaction (p = 0.038) whereby ACR Cho was 26.7% lower in ADHD+PAE than in ADHD−PAE children (p < 0.0005), but there was no significant ACR Cho difference between non‐ADHD+PAE and non‐ADHD−PAE children. Voxelwise false‐discovery rate (FDR)‐corrected analysis of DTI revealed significantly (q ≤ 0.0101–0.05) lower FA in ACR for subjects with PAE (ADHD+PAE or non‐ADHD+PAE) than for subjects without PAE (ADHD−PAE or non‐ADHD−PAE). There was no significant effect of ADHD on FA. Thus, in overlapping samples, effects of PAE on Cho and FA were observed in the same white‐matter tract.
Conclusions
These findings point to tract focal, white‐matter pathology possibly specific for ADHD+PAE subjects. Low Cho may derive from abnormal choline metabolism; low FA suggests suboptimal white‐matter integrity in PAE. More advanced MRSI and DTI—and neurocognitive assessments—may better distinguish ADHD+PAE from ADHD−PAE, helping identify covert cases of FASD.
Autism is a developmental disorder of unknown neurologic basis. Based on prior work, we used proton magnetic resonance spectroscopic imaging (1H- MRSI) to investigate brain structures, including ...cingulate and caudate, that we hypothesized would reveal metabolic abnormalities in subjects with autism.
In 22 children with autism, 5 to 16 years old, and 20 age-matched healthy control subjects, 1H-MRSI assessed levels of N-acetyl compounds (NAA), choline compounds (Cho), and creatine plus phosphocreatine (Cr) at 272 msec echo-time and 1.5 T.
In subjects with autism compared with control subjects, Cho was 27.2% lower in left inferior anterior cingulate and 19.1% higher in the head of the right caudate nucleus; Cr was 21.1% higher in the head of the right caudate nucleus, but lower in the body of the left caudate nucleus (17.9%) and right occipital cortex (16.6%).
Results are consistent with altered membrane metabolism, altered energetic metabolism, or both in the left anterior cingulate gyrus, both caudate nuclei, and right occipital cortex in subjects with autism compared with control subjects.
Motexafin gadolinium (MGd) is a putative radiation enhancer initially evaluated in patients with brain metastases. This Phase I trial studied the safety and tolerability of a 2-6-week course (10-22 ...doses) of MGd with radiotherapy for glioblastoma multiforme.
A total of 33 glioblastoma multiforme patients received one of seven MGd regimens starting at 10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10 daily doses then three times per week). The National Cancer Institute Cancer Therapy Evaluation Program toxicity and stopping rules were applied.
The maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times per week) for 22 doses. The dose-limiting toxicity was reversible transaminase elevation. Adverse reactions included rash/pruritus (45%), chills/fever (30%), and self-limiting vesiculobullous rash of the thumb and fingers (42%). The median survival of 17.6 months prompted a case-matched analysis. In the case-matched analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared with the matched Radiation Therapy Oncology Group database patients with a median survival of 11.8 months (hazard ratio, 0.43; 95% confidence interval, 0.20-0.94).
The maximal tolerated dose of MGd with radiotherapy for glioblastoma multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then three times weekly). The baseline survival calculations suggest progression to Phase II trials is appropriate, with the addition of MGd to radiotherapy with concurrent and adjuvant temozolomide.
Growing evidence points to persistent neurological injury in chronic HIV infection. It remains unclear whether chronically HIV-infected individuals on combined antiretroviral therapy (cART) develop ...progressive brain injury and impaired neurocognitive function despite successful viral suppression and immunological restoration. In a longitudinal neuroimaging study for the HIV Neuroimaging Consortium (HIVNC), we used tensor-based morphometry to map the annual rate of change of regional brain volumes (mean time interval 1.0 ± 0.5 yrs), in 155 chronically infected and treated HIV+ participants (mean age 48.0 ± 8.9 years; 83.9% male) . We tested for associations between rates of brain tissue loss and clinical measures of infection severity (nadir or baseline CD4+ cell count and baseline HIV plasma RNA concentration), HIV duration, cART CNS penetration-effectiveness scores, age, as well as change in AIDS Dementia Complex stage. We found significant brain tissue loss across HIV+ participants, including those neuro-asymptomatic with undetectable viral loads, largely localized to subcortical regions. Measures of disease severity, age, and neurocognitive decline were associated with greater atrophy. Chronically HIV-infected and treated individuals may undergo progressive brain tissue loss despite stable and effective cART, which may contribute to neurocognitive decline. Understanding neurological complications of chronic infection and identifying factors associated with atrophy may help inform strategies to maintain brain health in people living with HIV.
The goal of this study was to develop a computer-aided therapeutic response (CADrx) system for early prediction of drug treatment response for glioblastoma multiforme (GBM) brain tumors with ...diffusion weighted (DW) MR images. In conventional Macdonald assessment, tumor response is assessed nine weeks or more post-treatment. However, we will investigate the ability of DW-MRI to assess response earlier, at five weeks post treatment. The apparent diffusion coefficient (ADC) map, calculated from DW images, has been shown to reveal changes in the tumor’s microenvironment preceding morphologic tumor changes. ADC values in treated brain tumors could theoretically both increase due to the cell kill (and thus reduced cell density) and decrease due to inhibition of edema. In this study, we investigated the effectiveness of features that quantify changes from pre- and post-treatment tumor ADC histograms to detect treatment response. There are three parts to this study: first, tumor regions were segmented on T1w contrast enhanced images by Otsu’s thresholding method, and mapped from T1w images onto ADC images by a 3D region of interest (ROI) mapping tool using DICOM header information; second, ADC histograms of the tumor region were extracted from both pre- and five weeks post-treatment scans, and fitted by a two-component Gaussian mixture model (GMM). The GMM features as well as standard histogram-based features were extracted. Finally, supervised machine learning techniques were applied for classification of responders or non-responders. The approach was evaluated with a dataset of 85 patients with GBM under chemotherapy, in which 39 responded and 46 did not, based on tumor volume reduction. We compared adaBoost, random forest and support vector machine classification algorithms, using ten-fold cross validation, resulting in the best accuracy of 69.41% and the corresponding area under the curve (Az) of 0.70.
The authors tested the hypothesis that proton magnetic resonance spectroscopy (1H-MRS) imaging can be used as a supportive diagnostic tool to differentiate clinically stable brain tumors from those ...progressing as a result of low- to high-grade malignant transformation or posttherapeutic recurrence. Twenty-seven patients with cerebral gliomas verified on histological examination were studied repeatedly with 1H-MRS imaging over a period of 3.5 years. At the time of each 1H-MRS imaging study, clinical examination, MR imaging, positron emission tomography with 18F-fluorodeoxyglucose, and biopsy findings (when available) were used to categorize each patient as having either stable or progressive disease. Measures of the percentage changes in the choline (Cho) 1H-MRS imaging signal intensity between studies, which were obtained without knowledge of the clinical categorization, allowed the investigators to segregate the groups with a high degree of statistical significance. All progressive cases showed a Cho signal increase between studies of more than 45%, whereas all stable cases showed an elevation of less than 35%, no change, or even a decreased signal. The authors conclude that increased Cho levels coincide with malignant degeneration of cerebral gliomas and therefore may possibly be used as a supportive indicator of progression of these neoplasms.
Abstract only BACKGROUND: Despite its proven efficacy in acute ischemic stroke, thrombolytic treatment rates are exceedingly low. A common barrier is a prerequisite estimation of finite event ...duration. Whole-brain MR DWI-FLAIR comparative methods of hyperacute-acute ischemic match/mismatch are currently under investigation as a potential surrogate for unknown duration. Profiles that reflect field ischemia but not viability may not detect important voxel-level heterogeneity and, consequently, areas that may potentially benefit from revascularization. Voxel-based MR methods that assess viability (PWI) and ischemia (DWI-FLAIR) may afford a more informative measure to determine and expand treatment eligibility. METHODS: Consecutive, treated M1 ischemic stroke patients with serial MRI were analyzed with voxel-based, volumetric measures of DWI, FLAIR, and PWI for match/mismatch. Co-registration of Day 0 DWI, PWI, and FLAIR with Day 5/discharge FLAIR was then followed by ROI analysis of the affected MCA field. Day 0 DWI, PWI, FLAIR and Day 5/discharge FLAIR voxels were pooled into average populations according to positivity. Serial voxel-populations were then quantified at Day 0 and at Day 5/discharge individually and group-wise. Data processing and analysis were performed with MatLab, 3DSlicer, and Microsoft Excel. RESULTS: 38 treated M1 occlusive patients (mean age 65 years, 25 female) underwent a voxel-based analysis of DWI, PWI, and FLAIR at day 0 and FLAIR at day5/discharge. At baseline, 93% of the affected MCA field was DWI-/PWI+/FLAIR-; 7% was DWI+/PWI+/FLAIR-; and ~3% was FLAIR+. At day 5/discharge, 36% of baseline at-risk field (DWI-/PWI+); >95% of baseline field undergoing ischemia (DWI+/PWI+); and 94% of baseline ischemic tissue (FLAIR+) were FLAIR+. CONCLUSIONS: Voxel-based analyses of DWI, PWI and FLAIR on serial MRI reveal heterogeneity of voxel status at baseline and in tissue fate, and provide a dynamic tissue profile in treated M1 ischemic stroke. Over 1/3 of baseline viable tissue became ischemic at day 5 suggesting nearly 2/3 of the field remained viable. Future evaluations of voxel-based approaches that profile viability and ischemia are warranted to validate this methodology and its potential to expand acute stroke treatment eligibility.
Short-interval scanning of patients offers a detailed understanding of the natural progression of tumor tissue, as revealed through imaging markers such as contrast enhancement and edema, prior to ...therapy. Following treatment, short-interval scanning can also provide evidence of attenuation of growth rates. We present a longitudinal imaging study of a patient with glioblastoma multiforme (GBM) scanned 15 times in 104 days on a 3 T MR scanner. Images were analyzed independently by two automated algorithms capable of creating detailed maps of tumor changes as well as volumetric analysis. The algorithms, a nearest-neighbor-based tissue segmentation and a surface-modeling algorithm, tracked the patient's response to temozolomide, showing an attenuation of growth. The need for surrogate imaging end-points, of which growth rates are an example, is discussed. Further, the strengths of these algorithms, the insight gained by short-interval scanning, and the need for a better understanding of imaging markers are also described.
This trial assessed the value of brain imaging to guide treatment for stroke. Clinical outcomes with embolectomy were not superior to those with standard care in all patients or in the subgroup ...identified by brain imaging as most likely to benefit from embolectomy.
Multiple randomized, controlled trials have shown the efficacy of the use of intravenous tissue plasminogen activator (t-PA), administered up to 4.5 hours after the onset of symptoms of acute ischemic stroke.
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However, the global effect of this therapy has been limited, largely because of the narrow time window available for treatment and the risk of symptomatic intracerebral hemorrhage. Although endovascular approaches, including thrombectomy devices, have been shown to achieve greater rates of recanalization than the use of intravenous t-PA, no randomized, controlled trial has been completed comparing clinical outcomes versus standard medical care. Moreover, the potential to benefit from . . .
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