Faculty Bibliography

PURPOSE: The aim of this study was to use intravoxel incoherent motion diffusion-weighted imaging to discriminate subtypes of renal neoplasms and to assess agreement between intravoxel incoherent motion (perfusion fraction, fp) and dynamic contrast-enhanced magnetic resonance imaging (MRI) metrics of tumor vascularity. SUBJECTS AND METHODS: In this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved prospective study, 26 patients were imaged at 1.5-T MRI using dynamic contrast-enhanced MRI with high temporal resolution and diffusion-weighted imaging using 8 b values (range, 0-800 s/mm). Perfusion fraction (fp), tissue diffusivity (Dt), and pseudodiffusivity (Dp) were calculated using biexponential fitting of the diffusion data. Apparent diffusion coefficient (ADC) was calculated with monoexponential fit using 3 b values of 0, 400, and 800 s/mm. Dynamic contrast-enhanced data were processed with a semiquantitative method to generate model-free parameter cumulative initial area under the curve of gadolinium concentration at 60 seconds (CIAUC60). Perfusion fraction, Dt, Dp, ADC, and CIAUC60 were compared between different subtypes of renal lesions. Perfusion fraction was correlated with CIAUC60. RESULTS: We examined 14 clear cell, 4 papillary, 5 chromophobe, and 3 cystic renal cell carcinomas (RCCs). Although fp had higher accuracy (area under the curve, 0.74) for a diagnosis of clear cell RCC compared with Dt or ADC, the combination of fp and Dt had the highest accuracy (area under the curve, 0.78). The combination of fp and Dt diagnosed papillary RCC and cystic RCC with 100% accuracy, and clear cell RCC and chromophobe RCC, with 86.5% accuracy. There was significant strong correlation between fp and CIAUC60 (r = 0.82; P < 0.001). CONCLUSION: Intravoxel incoherent motion parameters fp and Dt can discriminate renal tumor subtypes. Perfusion fraction demonstrates good correlation with CIAUC60 and can assess degree of tumor vascularity without the use of exogenous contrast agent.

Many visual and auditory neurons have response properties that are well explained by pooling the rectified responses of a set of spatially shifted linear filters. These filters cannot be estimated using spike-triggered averaging (STA). Subspace methods such as spike-triggered covariance (STC) can recover multiple filters, but require substantial amounts of data, and recover an orthogonal basis for the subspace in which the filters reside rather than the filters themselves. Here, we assume a linear-nonlinear-linear-nonlinear (LN-LN) cascade model in which the first linear stage is a set of shifted ('convolutional') copies of a common filter, and the first nonlinear stage consists of rectifying scalar nonlinearities that are identical for all filter outputs. We refer to these initial LN elements as the 'subunits' of the receptive field. The second linear stage then computes a weighted sum of the responses of the rectified subunits. We present a method for directly fitting this model to spike data, and apply it to both simulated and real neuronal data from primate V1. The subunit model significantly outperforms STA and STC in terms of cross-validated accuracy and efficiency.

Publisher: Abstract available from the publisher.

CONTEXT Prospective studies of childhood attention-deficit/hyperactivity disorder (ADHD) have not extended beyond early adulthood. OBJECTIVE To examine whether children diagnosed as having ADHD at a mean age of 8 years (probands) have worse educational, occupational, economic, social, and marital outcomes and higher rates of ongoing ADHD, antisocial personality disorder (ASPD), substance use disorders (SUDs), adult-onset psychiatric disorders, psychiatric hospitalizations, and incarcerations than non-ADHD comparison participants at a mean age of 41 years. DESIGN Prospective, 33-year follow-up study, with masked clinical assessments. SETTING Research clinic. PARTICIPANTS A total of 135 white men with ADHD in childhood, free of conduct disorder, and 136 men without childhood ADHD (65.2% and 76.4% of original cohort, respectively). MAIN OUTCOME MEASURES Occupational, economic, and educational attainment; marital history; occupational and social functioning; ongoing and lifetime psychiatric disorders; psychiatric hospitalizations; and incarcerations. RESULTS Probands had significantly worse educational, occupational, economic, and social outcomes; more divorces; and higher rates of ongoing ADHD (22.2% vs 5.1%, P < .001), ASPD (16.3% vs 0%, P < .001), and SUDs (14.1% vs 5.1%, P = .01) but not more mood or anxiety disorders (P = .36 and .33) than did comparison participants. Ongoing ADHD was weakly related to ongoing SUDs (varphi = 0.19, P = .04), as well as ASPD with SUDs (varphi = 0.20, P = .04). During their lifetime, probands had significantly more ASPD and SUDs but not mood or anxiety disorders and more psychiatric hospitalizations and incarcerations than comparison participants. Relative to comparisons, psychiatric disorders with onsets at 21 years or older were not significantly elevated in probands. Probands without ongoing psychiatric disorders had worse social, but not occupational, functioning. CONCLUSIONS The multiple disadvantages predicted by childhood ADHD well into adulthood began in adolescence, without increased onsets of new disorders after 20 years of age. Findings highlight the importance of extended monitoring and treatment of children with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder of childhood. Preliminary studies with proton magnetic resonance spectroscopy ((1)H-MRS) of the brain have reported differences in brain metabolite concentration-to-Cr ratios between individuals with ADHD and unaffected controls in several frontal brain regions including anterior cingulate cortex. Using multivoxel (1)H-MRS, we compared 14 individuals affected with ADHD to 20 individuals without ADHD from the same genetic isolate. After controlling by sex, age, and multiple testing, we found significant differences at the right posterior cingulate of the Glx/Cr ratio density distribution function between ADHD cases and controls (P < 0.05). Furthermore, we found several interactions of metabolite concentration-to-Cr ratio, age, and ADHD status: Ins/Cr and Glx/Cr ratios at the left posterior cingulate, and NAA/Cr at the splenius, right posterior cingulate, and at the left posterior cingulate. We also found a differential metabolite ratio interaction between ADHD cases and controls for Ins/Cr and NAA/Cr at the right striatum. These results show that: (1) NAA/Cr, Glx/Cr, and Ins/Cr ratios, as reported in other studies, exhibit significant differences between ADHD cases and controls; (2) differences of these metabolite ratios between ADHD cases and controls evolve in specific and recognizable patterns throughout age, a finding that replicates previous results obtained by structural MRI, where is demonstrated that brain ontogeny follows a different program in ADHD cases and controls; (3) Ins/Cr and NAA/Cr ratios, at the right striatum, interact in a differential way between ADHD cases and controls. As a whole, these results replicate previous 1H-MRS findings and add new intriguing differential metabolic and ontogeny patterns between ADHD cases and controls that warrant further pursue.

Since the brain's gray matter (GM) and white matter (WM) metabolite concentrations differ, their partial volumes can vary the voxel's (1) H MR spectroscopy ((1) H-MRS) signal, reducing sensitivity to changes. While single-voxel (1) H-MRS cannot differentiate between WM and GM signals, partial volume correction is feasible by MR spectroscopic imaging (MRSI) using segmentation of the MRI acquired for VOI placement. To determine the magnitude of this effect on metabolic quantification, we segmented a 1-mm(3) resolution MRI into GM, WM and CSF masks that were co-registered with the MRSI grid to yield their partial volumes in approximately every 1 cm(3) spectroscopic voxel. Each voxel then provided one equation with two unknowns: its i- metabolite's GM and WM concentrations C(i) (GM) , C(i) (WM) . With the voxels' GM and WM volumes as independent coefficients, the over-determined system of equations was solved for the global averaged C(i) (GM) and C(i) (WM) . Trading off local concentration differences offers three advantages: (i) higher sensitivity due to combined data from many voxels; (ii) improved specificity to WM versus GM changes; and (iii) reduced susceptibility to partial volume effects. These improvements made no additional demands on the protocol, measurement time or hardware. Applying this approach to 18 volunteered 3D MRSI sets of 480 voxels each yielded N-acetylaspartate, creatine, choline and myo-inositol C(i) (GM) concentrations of 8.5 +/- 0.7, 6.9 +/- 0.6, 1.2 +/- 0.2, 5.3 +/- 0.6mM, respectively, and C(i) (WM) concentrations of 7.7 +/- 0.6, 4.9 +/- 0.5, 1.4 +/- 0.1 and 4.4 +/- 0.6mM, respectively. We showed that unaccounted voxel WM or GM partial volume can vary absolute quantification by 5-10% (more for ratios), which can often double the sample size required to establish statistical significance