M. Albert Thomas

Decreased anterior cingulate myo-inositol/creatine spectroscopy resonance with lithium treatment in children with bipolar disorder.

This project was designed to compare differences in brain proton spectra between children and adolescents with bipolar disorder (BPD) and gender and age-matched normal controls, and to measure changes in myo-inositol levels following lithium therapy, utilizing in vivo proton magnetic resonance spectroscopy (1H MRS). A single voxel (2x2x2 cm3) was placed in brain anterior cingulate cortex for acquisition of the 1H spectra at baseline and after acute (∼7 days) lithium administration in 11 children (mean age 11.4 years) diagnosed with BPD, and in 11 normal controls. Acute lithium treatment was associated with a significant reduction in the myo-inositol/creatine ratio. This decrement was also significant in lithium-responders when analyzed separate from non-responders. Compared to normal controls, BPD subjects showed a trend towards a higher myo-inositol/creatine during the manic phase. These preliminary data provide evidence that a significant reduction in anterior cingulate myo-inositol magnetic resonance may occur after lithium treatment, especially among responders. Follow-up studies involving a larger sample may allow us to confirm whether changes in myo-inositol associated with acute lithium therapy persist in long-term clinical response of patients with and without lithium compliance.

Hippocampal Changes Associated with Early-Life Adversity and Vulnerability to Depression

BACKGROUND Smaller hippocampal volume has been reported in some adult and pediatric studies of unipolar major depressive disorder. It is not clear whether the smaller hippocampal volume precedes or is a consequence of the illness. Early-life adversity is associated with both smaller hippocampal volume and increased vulnerability to depressive disorder. Hippocampal changes may mediate the relationship between early-life adversity and depressive illness in a subset of patients. However, there are no reports of longitudinal clinical studies that have examined this issue. METHODS Thirty adolescents with unipolar major depressive disorder, 22 adolescent volunteers with no personal history of a psychiatric illness including depression but who were at high risk for developing depression by virtue of parental depression (high-risk group), and 35 adolescent volunteers with no personal or family history of a psychiatric disorder (control subjects) underwent volumetric magnetic resonance imaging studies. Information was also gathered on early and recent adverse experiences with standard interviews. The participants were followed for up to 5 years to assess the onset and clinical course of depression. RESULTS Depressed and high-risk groups had significantly smaller left and right hippocampal volumes than control subjects. Higher levels of early-life adversity were associated with smaller hippocampal volumes. Smaller hippocampal volume partially mediated the effect of early-life adversity on depression during longitudinal follow-up. CONCLUSIONS Smaller hippocampal volume in adolescents at high risk for depression suggests that it may be a vulnerability marker for the illness. Early-life adversity may interact with genetic vulnerability to induce hippocampal changes, potentially increasing the risk for depressive disorder.

Increased anterior cingulate/medial prefrontal cortical glutamate and creatine in bipolar depression

Proton magnetic resonance spectroscopy (1HMRS) is an in vivo brain imaging method that can be used to investigate psychotropic drug mechanism of action. This study evaluated baseline 1HMRS spectra of bipolar depressed patients and whether the level of cerebral metabolites changed after an open trial of lamotrigine, an anti-glutamatergic mood stabilizer. Twenty-three bipolar depressed and 12 control subjects underwent a MRS scan of the anterior cingulate/medial prefrontal cortex. The scan was performed on a GE whole-body 1.5 T MRI scanner using single-voxel PRESS (TE/TR=30/3000 ms, 3 × 3 × 3 cm3 and post-processed offline with LCModel. Baseline CSF-corrected absolute concentrations of glutamate+glutamine ([Glx]), glutamate ([Glu]), and creatine+phosphocreatine ([Cr]) were significantly higher in bipolar depressed subjects vs healthy controls. The non-melancholic subtype had significantly higher baseline [Glx] and [Glu] levels than the melancholic subtype. Remission with lamotrigine was associated with significantly lower post-treatment glutamine ([Gln]) in comparison to non-remission. These data suggest that non-melancholic bipolar depression is characterized by increased glutamate coupled with increased energy expenditure. Lamotrigine appears to reduce glutamine levels associated with treatment remission. Further study is encouraged to determine if these MR spectroscopic markers can delineate drug mechanism of action and subsequent treatment response.

Localized 2D J-resolved 1H MR spectroscopy : strong coupling effects in vitro and in vivo

A two-dimensional (2D) J-resolved MR spectroscopy sequence (2D J-PRESS), fully localized in three dimensions, has been implemented on a whole-body MR scanner. A modified PRESS sequence with [90 degrees-180 degrees-t1/2-180 degrees-t1/2-acquisition] was used for voxel localization. An incremental delay (t1/2) was added to the intervals before and after the last slice-selective 180 degree RF pulse to monitor the J-evolution in a localized 2D MR spectrum. Spectra were recorded with phantoms containing common cerebral metabolites--alanine, N-acetyl aspartate, glutamine, glutamate, taurine, myo-inositol, glucose, aspartate, GABA, and choline at 50 mM. In conformity with previously reported results, additional cross-peaks due to strong coupling were monitored in many metabolites. A brain phantom was developed to mimic the gray matter of human brain with the metabolites at physiological concentrations (0.5-12 mM). In vivo 2D J-PRESS spectra (n = 18) of healthy human brain were in conformity with those recorded from the brain phantom.

Measurement of brain metabolites in patients with type 2 diabetes and major depression using proton magnetic resonance spectroscopy

Type 2 diabetes and major depression are disorders that are mutual risk factors and may share similar pathophysiological mechanisms. To further understand these shared mechanisms, the purpose of our study was to examine the biochemical basis of depression in patients with type 2 diabetes using proton MRS. Patients with type 2 diabetes and major depression (n=20) were scanned along with patients with diabetes alone (n=24) and healthy controls (n=21) on a 1.5 T MRI/MRS scanner. Voxels were placed bilaterally in dorsolateral white matter and the subcortical nuclei region, both areas important in the circuitry of late-life depression. Absolute values of myo-inositol, creatine, N-acetyl aspartate, glutamate, glutamine, and choline corrected for CSF were measured using the LC-Model algorithm. Glutamine and glutamate concentrations in depressed diabetic patients were significantly lower (p<0.001) in the subcortical regions as compared to healthy and diabetic control subjects. Myo-inositol concentrations were significantly increased (p<0.05) in diabetic control subjects and depressed diabetic patients in frontal white matter as compared to healthy controls. These findings have broad implications and suggest that alterations in glutamate and glutamine levels in subcortical regions along with white matter changes in myo-inositol provide important neurobiological substrates of mood disorders.

Use of MR imaging to determine preservation of the neurovascular bundles at robotic-assisted laparoscopic prostatectomy.

PURPOSE To determine whether findings at preoperative endorectal coil magnetic resonance (MR) imaging influence the decision to preserve neurovascular bundles and the extent of surgical margins in robotic-assisted laparoscopic prostatectomy (RALP). MATERIALS AND METHODS This study was approved by the investigational review board and was compliant with the HIPAA; the requirement to obtain informed consent was waived. The authors prospectively evaluated 104 consecutive men with biopsy-proved prostate cancer who underwent preoperative endorectal coil MR imaging of the prostate and subsequent RALP. MR imaging was performed at 1.5 T between January 2004 and April 2008 and included T2-weighted imaging (n = 104), diffusion-weighted imaging (n = 88), dynamic contrast-enhanced imaging (n = 51), and MR spectroscopy (n = 91). One surgeon determined the planned preoperative extent of resection bilaterally on the basis of clinical information and then again after review of the final MR imaging report. The differences in the surgical plan before and after review of the MR imaging report were determined and compared with the actual surgical and pathologic results by using logistic regression analysis. Continuous and ranked variables underwent Pearson and Spearman analysis. RESULTS After review of MR imaging results, the initial surgical plan was changed in 28 of the 104 patients (27%); the surgical plan was changed to a nerve-sparing technique in 17 of the 28 patients (61%) and to a non-nerve-sparing technique in 11 (39%). Seven of the 104 patients (6.7%) had positive surgical margins. In patients whose surgical plan was changed to a nerve-sparing technique, there were no positive margins on the side of the prostate with a change in treatment plan. CONCLUSION Preoperative prostate MR imaging data changed the decision to use a nerve-sparing technique during RALP in 27% of patients in this series.

Volume-localized two-dimensional correlated magnetic resonance spectroscopy of human breast cancer.

A localized 2D correlation spectroscopic sequence (L‐COSY) was implemented and applied in human breast cancer in vivo to evaluate the water to fat (both saturated and unsaturated) ratios and also to identify choline. Being in agreement with the conventional 1D magnetic resonance spectroscopy (MRS) results, elevated water to lipids ratios were found in breast cancers and choline was observed only in a few cancer patients. J. Magn. Reson. Imaging 2001;14:181–186.

Cerebral diffusion tensor imaging and in vivo proton magnetic resonance spectroscopy in patients with fulminant hepatic failure

Background and Aim:  Cerebral edema is a major complication in patients with fulminant hepatic failure (FHF). The aim of this study was to evaluate the metabolite alterations and cerebral edema in patients with FHF using in vivo proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging, and to look for its reversibility in survivors.

Neurochemistry of late‐life major depression: A pilot two‐dimensional MR spectroscopic study

To evaluate a two‐dimensional localized chemical shift correlated spectroscopy (L‐COSY) sequence in elderly patients with major depression.

Correlation of Gleason Scores with Diffusion-Weighted Imaging Findings of Prostate Cancer

The purpose of our study was to compare the apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging (DWI) of prostate cancer (PCa) patients with three classes of pathological Gleason scores (GS). Patients whose GS met these criteria (GS 3 + 3, GS 3 + 4, and GS 4 + 3) were included in this study. The DWI was performed using b values of 0, 50, and 400 s/mm2 in 44 patients using an endorectal coil on a 1.5T MRI scanner. The apparent diffusion coefficient (ADC) values were calculated from the DWI data of patients with three different Gleason scores. In patients with a high-grade Gleason score (4 + 3), the ADC values were lower in the peripheral gland tissue, pathologically determined as tumor compared to low grade (3 + 3 and 3 + 4). The mean and standard deviation of the ADC values for patients with GS 3 + 3, GS 3 + 4, and GS 4 + 3 were 1.135 ± 0.119, 0.976 ± 0.103 and 0.831 ± 0.087 mm2/sec. The ADC values were statistically significant (P < 0.05) between the three different scores with a trend of decreasing ADC values with increasing Gleason scores by one-way ANOVA method. This study shows that the DWI-derived ADC values may help differentiate aggressive from low-grade PCa.