Albert Thomas

Focal Subcortical Biophysical Abnormalities in Patients Diagnosed With Type 2 Diabetes and Depression

CONTEXT Major depressive disorder has been consistently identified in patients with type 2 diabetes. Despite its high prevalence and clinical effect, the neurobiological substrates underlying depression in patients with diabetes remain largely unknown. OBJECTIVE To examine the biophysical integrity of proteins in critical white and gray matter regions in patients with type 2 diabetes and major depression to understand the pathophysiology of depression in diabetes. DESIGN A cross-sectional magnetization transfer study using magnetic resonance imaging. Regions examined included the anterior cingulate, corpus callosum, frontal and occipital white matter, and the caudate and lenticular nuclei. SETTING A tertiary care university hospital. PARTICIPANTS We studied 16 patients diagnosed with type 2 diabetes and major depression, 22 patients diagnosed with diabetes without depression (diabetic controls), and 30 controls without diabetes or major depression (healthy controls). MAIN OUTCOME MEASURES Magnetization transfer ratios, a measure of the biophysical structure of proteins in the gray and white matter. RESULTS Magnetization transfer ratios were significantly lower bilaterally in the head of the caudate nucleus in the group with diabetes and depression compared with the other 2 groups (P < .001). Diabetic controls had values between the depressed diabetic and healthy control groups. There were no significant differences in magnetization transfer ratios between groups in the other regions examined. CONCLUSIONS These data indicate that there is an important subcortical biophysical component to depression in patients with type 2 diabetes. This finding has broad implications for the neuronal circuitry underlying mood disorders.

Radical prostatectomy: value of prostate MRI in surgical planning

The introduction of serum prostate-specific antigen to the prostate cancer screening algorithm has led to an increase in prostate cancer diagnosis as well as a migration toward lower-stage cancer at the time of diagnosis. This stage migration has coincided with changes in treatment options; these include active surveillance, new therapies, and advances in surgical techniques. Use of robot-assisted radical prostatectomy (RARP) as a surgical technique has seen a significant increase over the past several years: the number of patients undergoing RARP has risen from 1% to 40% of all prostatectomies from 2001–2006 to as many as 80% in 2010. The robotic interface provides a 3D magnified view of the surgical field, intuitive instrument manipulation, motion scaling, tremor filtration, and excellent dexterity and range of motion. However, in some cases, the lack of tactile (haptic) feedback may limit the surgeon’s decision making ability in assessing malignant involvement of the neurovascular bundles. Pre-operative planning relies on nomograms based on limited clinical and prostate biopsy information. The surgical decision to spare or resect the neurovascular bundles is based on clinical information which is not spatially or anatomically based. Advances in magnetic resonance imaging (MRI) may provide spatially localized information to fill this void and aid surgical planning, particularly for robotic surgeons. In this review, we discuss the potential role of pre-operative MRI in surgical planning for radical prostatectomy.

Prefrontal myo-inositol concentration and visuospatial functioning among diabetic depressed patients

Patients with diabetes mellitus are reported to be at higher risk for developing neuropsychiatric disorders such as dementia and depression. Myo-inositol (mI), a neuronal/glial metabolite associated with multiple functions in the brain, has been shown to be increased in cognitive disorders, depression and diabetes. This study examined whether elevations in dorsolateral (DL) mI of diabetic patients with depression were associated with visuospatial deficits. Diabetic and depressed patients (n=18) were matched with patients with diabetes but without depression (n=20) and control subjects (n=19). Subjects were scored on both the recall and recognition tasks of the Rey-Osterreith Complex Figure (ROCF). Proton magnetic spectroscopy spectra from bilateral prefrontal white matter voxels were used to obtain concentrations of mI. Controls showed negative correlations between mI in right DL white matter and recall and recognition subtests. No correlation was observed for depressed diabetic patients. Correlations for diabetic controls fell midway between the comparison and depressed diabetic groups. The expected pattern of association between mI and visuospatial impairment in the right DL prefrontal region was seen among healthy controls. Progressive weakening of this association across both diabetic groups might be related to progressive changes in neural activity that underlies visuospatial function.

Accelerating dynamic magnetic resonance imaging (MRI) for lung tumor tracking based on low-rank decomposition in the spatial-temporal domain: a feasibility study based on simulation and preliminary prospective undersampled MRI.

PURPOSE To evaluate a low-rank decomposition method to reconstruct down-sampled k-space data for the purpose of tumor tracking. METHODS AND MATERIALS Seven retrospective lung cancer patients were included in the simulation study. The fully-sampled k-space data were first generated from existing 2-dimensional dynamic MR images and then down-sampled by 5 × -20 × before reconstruction using a Cartesian undersampling mask. Two methods, a low-rank decomposition method using combined dynamic MR images (k-t SLR based on sparsity and low-rank penalties) and a total variation (TV) method using individual dynamic MR frames, were used to reconstruct images. The tumor trajectories were derived on the basis of autosegmentation of the resultant images. To further test its feasibility, k-t SLR was used to reconstruct prospective data of a healthy subject. An undersampled balanced steady-state free precession sequence with the same undersampling mask was used to acquire the imaging data. RESULTS In the simulation study, higher imaging fidelity and low noise levels were achieved with the k-t SLR compared with TV. At 10 × undersampling, the k-t SLR method resulted in an average normalized mean square error <0.05, as opposed to 0.23 by using the TV reconstruction on individual frames. Less than 6% showed tracking errors >1 mm with 10 × down-sampling using k-t SLR, as opposed to 17% using TV. In the prospective study, k-t SLR substantially reduced reconstruction artifacts and retained anatomic details. CONCLUSIONS Magnetic resonance reconstruction using k-t SLR on highly undersampled dynamic MR imaging data results in high image quality useful for tumor tracking. The k-t SLR was superior to TV by better exploiting the intrinsic anatomic coherence of the same patient. The feasibility of k-t SLR was demonstrated by prospective imaging acquisition and reconstruction.

Proton magnetic resonance spectroscopy of human cervical spondylosis at 3T

Study design:A single-center magnetic resonance imaging and spectroscopic study involving 21 patients with advanced cervical spondylosis and 11 healthy controls.Objective:We assessed the utility of magnetic resonance spectroscopy (MRS) to quantify biochemical changes within the spinal cord and serve as a potential biomarker in patients with cervical spondylosis with or without T2 hyperintensity within the cord.Setting:Los Angeles, California, USA.Methods:Twenty-one patients with cervical spondylosis and eleven healthy controls were evaluated. Single-voxel MRS was performed in the cervical cord. Morphometry of the spinal canal space was measured. N-Acetyl aspartylglutamic acid (NAA), choline (Cho), myo-inositol (Myo-I), glutamine–glutamate complex (Glx) and lactate metabolite concentration ratios with respect to total creatine (Cr) were quantified using an LC model algorithm and compared between healthy controls and spondylosis patients. Correlation of MRS metabolites with modified Japanese Orthopaedic Association (mJOA) score was also performed.Results:The spinal canal space was significantly different between patients and controls (analysis of variance (ANOVA), P<0.0001). Total Cho-to-Cr ratio was significantly elevated in patients with spondylosis and T2-hyperintensity compared with healthy controls (ANOVA, P<0.01). A significantly higher Cho-to-NAA ratio was observed in spondylosis patients compared with healthy controls (ANOVA, P<0.01). Slightly elevated Glx and Myo-I were encountered in patients with stenosis without T2 hyperintensity. A linear correlation between Cho-NAA ratio and mJOA was also observed (P<0.01).Conclusion:MRS appears sensitive to biochemical changes occurring in advanced cervical spondylosis patients. The Cho/NAA ratio was significantly correlated with the mJOA score, providing a potentially clinically useful radiographical biomarker for the management of advanced cervical spondylosis patients.Sponsorship:NIH NINDS 1R21NS65419-1A1; NIH/NINDS 1R01NS078494-01A1.

WE‐G‐WAB‐04: Ultra‐Fast Dynamic MRI for Lung Tumor Tracking Based On Compressed Sensing and Low‐Rank Decomposition in the Spatial‐Temporal Domain

PURPOSE Dynamic MRI is an attractive tool for internal organ motion monitoring but its speed is yet to be improved for real time 3D imaging. The purpose of the study is to accelerate the imaging acquisition using a hybrid compressed-sensing and low rank decomposition method (k-t SLR) exploiting data sparsity in the spatial-temporal domain. METHODS Six retrospective lung cancer patients were included in the study. For each subject, 120 continuously dynamic 2D MR images were acquired using a fast steady state precession imaging sequence. To test the feasibility of accelerated MR acquisition, fully sampled k-space data were down-sampled by 5-20 folds before reconstruction. The under-sampled low rank spatial-temporal matrix was recovered by a k-t SLR method computing the matrix of minimum nuclear norm that fits the data. The k-t SLR results were compared against conventional total variation (TV) reconstruction of individual dynamic MR frames. RESULTS High imaging fidelity and low noise levels were achieved with the k-t SLR method even at the most aggressive down-sampling ratio while TV reconstruction showed substantial loss of details and subsequently greater tracking errors. The k-t SLR method resulted in an average normalized mean square error less than 0.05 as opposed to 0.23 by using the TV reconstruction on individual frames. In addition to the high correlation coefficients (>0.90) in the tumor trajectories automatically tracked from the original images and the k-t SLR reconstructed images, less than 6% points showed tracking errors greater than 1 mm with 20 fold down-sampling, as opposed to the lower correlation coefficient (0.87) and 15% tracking error from using TV alone with 10 fold data down-sampling. CONCLUSION We have demonstrated the potential to significantly reduce the amount data samples required for lung MR image reconstruction in the radiotherapy context where long imaging acquisition of a repetitive anatomic process is performed. The study is supported in part by NIH 1R21CA144063 and R21CA161670.

State-of-the-Art Imaging of Prostate Cancer

Prostate cancer is the second most common cancer diagnosed inAmerican men, with an estimate of 186,320 new cases in 2008 and an estimated death toll of 28,660 patients, a number surpassed only by lung cancer.1 Due to its high incidence rate, unpredictable behavior, and associated morbidity and mortality, many efforts have been made to detect prostate cancer at an early stage, through screening tests such as clinical digital rectal examination (DRE) and serum prostate-specific antigen (PSA) level.1 Currently, digital rectal examination is used both as a screening test and as a way to clinically stage prostate cancer by palpation of abnormal nodularity, asymmetry, or induration of the gland. This examination, however, is limited by significant inter-examiner variability and poor reproducibility, resulting in poor sensitivity and positive predictive value. Likewise, digital rectal examination can only palpate the posterior and lateral aspects of the prostate due to anatomic boundaries, limiting its accuracy and invariably missing lesions in other locations. Serum PSAlevels have been used as a screening test since the early 1990s. Levels above 4.0 ng/mL typically are considered abnormal. It is important to note that PSA levels can become elevated in benign conditions such as prostatitis and benign prostatic hyperplasia (BPH). Similarly, PSA levels may vary based on age and race, with higher levels found in African-American men. Such variability is reflected in the test’s high sensitivity yet low specificity for the diagnosis of prostate cancer. Due to the intrinsic limitations of both screening tests, patients with a high index of suspicion for prostate cancermust undergo transrectal ultrasound (TRUS)-guided biopsies of the prostate. In this procedure, the prostate is divided into sextants, and a total of 12 core biopsies (two per sextant) are analyzed. The cancer grade, based on theGleason score, is determined based on the degree of disordered growth of the prostate cancer. The treating physician uses theGleason score, in combinationwith clinical factors and PSA, to determine the best course of care. Currently, prostate cancer staging is done most commonly through prediction tools known as prostate nomograms,which take into consideration the patient’s serumPSAlevels,Gleason score, and DRE findings, but do not factor in actual tumor visualization. Clinical staging is based on the TNM classification nomenclature, which emphasizes whether the cancer is containedwithin the prostate (organ-confined) or if the cancer extends outside the prostate (extracapsular extension). Patientswith organ-confined cancer are offered curative treatment through surgical resection and/or systemic therapy. Patientswith tumor outside the prostate are considered to have systemic disease and are offered multimodal palliative treatment as away to control local and distant lesions.Determining whether prostate cancer is organ confined or has extracapsular extension (ECE) remains the most important differentiating factor in the workup and treatment of this disease. Accurate determination of the location, extent, and staging of prostate cancer is of great importance when planning surgical resection or medical treatment. For this reason, several imaging modalities, such as transrectal ultrasound and CT, havebeenused todiagnose and stageprostate cancer.Transrectal ultrasound alone usually is insufficient for detection of prostate cancer, because prostate cancer can appear as either a hypoechoic, echogenic, or isoechoic lesion. Likewise, CT imaging has been found to define prostate anatomy poorly, making State-of-the-Art Imaging of Prostate Cancer