Darryl Hwang

Solution of a Satisfiability Problem on a Gel-Based DNA Computer

We have succeeded in solving an instance of a 6-variable 11-clause 3-SAT problem on a gel-based DNA computer. Separations were performed using probes covalently bound to polyacrylamide gel. During the entire computation, DNA was retained within a single gel and moved via electrophoresis. The methods used appear to be readily automatable and should be suitable for problems of a significantly larger size.

Novel diffusion tensor imaging methodology to detect and quantify injured regions and affected brain pathways in traumatic brain injury

PURPOSE To develop and apply diffusion tensor imaging (DTI)-based normalization methodology for the detection and quantification of sites of traumatic brain injury (TBI) and the impact of injury along specific brain pathways in (a) individual TBI subjects and (b) a TBI group. MATERIALS AND METHODS Normalized DTI tractography was conducted in the native space of 12 TBI and 10 age-matched control subjects using the same number of seeds in each subject, distributed at anatomically equivalent locations. Whole-brain tracts from the control group were mapped onto the head of each TBI subject. Differences in the fractional anisotropy (FA) maps between each TBI subject and the control group were computed in a common space using a t test, transformed back to the individual TBI subjects head space, and thresholded to form regions of interest (ROIs) that were used to sort tracts from the control group and the individual TBI subject. Tract counts for a given ROI in each TBI subject were compared to group mean for the same ROI to quantify the impact of injury along affected pathways. The same procedure was used to compare the TBI group to the control group in a common space. RESULTS Sites of injury within individual TBI subjects and affected pathways included hippocampal/fornix, inferior fronto-occipital, inferior longitudinal fasciculus, corpus callosum (genu and splenium), cortico-spinal tracts and the uncinate fasciculus. Most of these regions were also detected in the group study. CONCLUSIONS The DTI normalization methodology presented here enables automatic delineation of ROIs within the heads of individual subjects (or in a group). These ROIs not only localize and quantify the extent of injury, but also quantify the impact of injury on affected pathways in an individual or in a group of TBI subjects.

Clinical Applications of Diffusion Tensor Imaging

Advancements in diffusion-weighted imaging during the past decade have led to the use of diffusion tensor imaging to further characterize the structural integrity of neural tissue and to noninvasively trace neuronal tracts in the brain and spine. This has led to many clinical applications that have aided in surgical planning for brain and spinal cord tumors and has increased the diagnostic potential of magnetic resonance imaging in disorders such as multiple sclerosis, Alzheimer disease, and traumatic brain injury.

Cortical Activation Associated with Muscle Synergies of the Human Male Pelvic Floor

Human pelvic floor muscles have been shown to operate synergistically with a wide variety of muscles, which has been suggested to be an important contributor to continence and pelvic stability during functional tasks. However, the neural mechanism of pelvic floor muscle synergies remains unknown. Here, we test the hypothesis that activation in motor cortical regions associated with pelvic floor activation are part of the neural substrate for such synergies. We first use electromyographic recordings to extend previous findings and demonstrate that pelvic floor muscles activate synergistically during voluntary activation of gluteal muscles, but not during voluntary activation of finger muscles. We then show, using functional magnetic resonance imaging (fMRI), that a region of the medial wall of the precentral gyrus consistently activates during both voluntary pelvic floor muscle activation and voluntary gluteal activation, but not during voluntary finger activation. We finally confirm, using transcranial magnetic stimulation, that the fMRI-identified medial wall region is likely to generate pelvic floor muscle activation. Thus, muscle synergies of the human male pelvic floor appear to involve activation of motor cortical areas associated with pelvic floor control.

Neuroimaging Changes in the Brain in Contact versus Noncontact Sport Athletes Using Diffusion Tensor Imaging

OBJECTIVE Traumatic brain injury in contact sports has significant impact on short-term neurologic and neurosurgical function as well as longer-term cognitive disability. In this study, we aim to demonstrate that contact sport participants exhibit differences in diffusion tensor imaging (DTI) caused by repeated physical impacts on the brain. We also aim to determine that impact incurred by the contact sports athletes during the season may result in the differences between the pre- and postseason DTI scans. METHODS DTI data were collected from 10 contact-sport (mean age 20.4 ± 1.36 years) and 13 age-matched noncontact-sport (mean age 19.5 ± 1.03 years) male athletes on a 3-Tesla magnetic resonance imaging scanner. A single-shot, echo-planar imaging sequence with b-value of 1000 s/mm(2) and 25 gradient directions was used. Eight of the athletes were again scanned after the end of the season. The b0 nondiffusion-weighted image was averaged five times. Voxel-wise, two-sample t tests were run for all group comparisons, and in each case, the positive false-discovery rate was computed to assess the whole-map, multiple-comparison corrected significance. RESULTS There were significant differences in the fractional anisotropy values in the inferior fronto-occipital fasciculus, parts of the superior and posterior coronal radiate, and the splenium of the corpus callosum (CC) as well as smaller clusters in the genu and parts of the body of the CC. In addition, the external capsule also shows some difference between the contact and noncontact athlete brains. In addition, the preseason and postseason showed differences in these regions, however, the postseason P-values show significance in more areas of the CC. CONCLUSIONS There are significant DTI changes in the CC, the external capsule, the inferior fronto-occipital fasciculus, as well as regions such as the superior/posterior corona radiata the preseason contact versus the noncontact control athletes were compared and also when the postseason contact athletes with the control athletes were compared.

Quantitative assessment of solid renal masses by contrast-enhanced ultrasound with time–intensity curves: how we do it

AbstractPurpose To discuss the evaluation of the enhancement curve over time of the major renal cell carcinoma (RCC) subtypes, oncocytoma, and lipid-poor angiomyolipoma, to aid in the preoperative differentiation of these entities. Differentiation of these lesions is important, given the different prognoses of the subtypes, as well as the desire to avoid resecting benign lesions.MethodsWe discuss findings from CT, MR, and US, but with a special emphasis on contrast-enhanced ultrasound (CEUS). CEUS technique is described, as well as time–intensity curve analysis.ResultsExamples of each of the major RCC subtypes (clear cell, papillary, and chromophobe) are shown, as well as examples of oncocytoma and lipid-poor angiomyolipoma. For each lesion, the time–intensity curve of enhancement on CEUS is reviewed, and correlated with the enhancement curve over time reported for multiphase CT and MR.ConclusionsPreoperative differentiation of the most common solid renal masses is important, and the time–intensity curves of these lesions show some distinguishing features that can aid in this differentiation. The use of CEUS is increasing, and as a modality it is especially well suited to the evaluation of the time–intensity curve.

Whole lesion quantitative CT evaluation of renal cell carcinoma: differentiation of clear cell from papillary renal cell carcinoma

PurposeClear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell cancer (RCC), followed by papillary RCC (pRCC). It is important to distinguish these two subtypes because of prognostic differences and possible changes in management, especially in cases undergoing active surveillance. The purpose of our study is to evaluate the use of voxel-based whole-lesion (WL) enhancement parameters on contrast enhanced computed tomography (CECT) to distinguish ccRCC from pRCC.Materials and methodsIn this institutional review board-approved study, we retrospectively queried the surgical database for post nephrectomy patients who had pathology proven ccRCC or pRCC and who had preoperative multiphase CECT of the abdomen between June 2009 and June 2011. A total of 61 patients (46 with ccRCC and 15 with pRCC) who underwent robotic assisted partial nephrectomy for clinically localized disease were included in the study. Multiphase CT acquisitions were transferred to a dedicated three-dimensional workstation, and WL regions of interest were manually segmented. Voxel-based contrast enhancement values were collected from the lesion segmentation and displayed as a histogram. Mean and median enhancement and histogram distribution parameters skewness, kurtosis, standard deviation, and interquartile range were calculated for each lesion. Comparison between ccRCC and pRCC was made using each imaging parameter. For mean and median enhancement, which had a normal distribution, independent t-test was used. For histogram distribution parameters, which were not normally distributed, Wilcoxon rank sum test was used.ResultsccRCC had significantly higher mean and median whole WL enhancement (p < 0.01) compared to pRCC on arterial, nephrographic, and excretory phases. ccRCC had significantly higher interquartile range and standard deviation (p < 0.01) and significantly lower skewness (p < 0.01) compared to pRCC on arterial and nephrographic phases. ccRCC had significantly lower kurtosis compared to pRCC on only the arterial phase.ConclusionOur study suggests that voxel-based WL enhancement parameters can be used as a quantitative tool to differentiate ccRCC from pRCC. Differentiating between the two main types of RCC would provide the patient and the treating physicians more information to formulate the initial approach to managing the patient’s renal cancer.

CT prediction of the Fuhrman grade of clear cell renal cell carcinoma (RCC): towards the development of computer-assisted diagnostic method

PurposeThere are distinct quantifiable features characterizing renal cell carcinomas on contrast-enhanced CT examinations, such as peak tumor enhancement, tumor heterogeneity, and percent contrast washout. While qualitative visual impressions often suffice for diagnosis, quantitative metrics if developed and validated can add to the information available from standard of care diagnostic imaging. The purpose of this study is to assess the use of quantitative enhancement metrics in predicting the Fuhrman grade of clear cell RCC.Materials and methods65 multiphase CT examinations with clear cell RCCs were utilized, 44 tumors with Fuhrman grades 1 or 2 and 21 tumors with grades 3 or 4. After tumor segmentation, the following data were extracted: histogram analysis of voxel-based whole lesion attenuation in each phase, enhancement and washout using mean, median, skewness, kurtosis, standard deviation, and interquartile range.ResultsStatistically significant difference was observed in 4 measured parameters between grades 1–2 and grades 3–4: interquartile range of nephrographic attenuation values, standard deviation of absolute enhancement, as well as interquartile range and standard deviation of residual nephrographic enhancement. Interquartile range of nephrographic attenuation values was 292.86 HU for grades 1–2 and 241.19 HU for grades 3–4 (p value 0.02). Standard deviation of absolute enhancement was 41.26 HU for grades 1–2 and 34.66 HU for grades 3–4 (p value 0.03). Interquartile range was 297.12 HU for residual nephrographic enhancement for grades 1–2 and 235.57 HU for grades 3–4 (p value 0.02), and standard deviation of the same was 42.45 HU for grades 1–2 and 37.11 for grades 3–4 (p value 0.04).ConclusionOur results indicate that absolute enhancement is more heterogeneous for lower grade tumors and that attenuation and residual enhancement in nephrographic phase is more heterogeneous for lower grade tumors. This represents an important step in devising a predictive non-invasive model to predict the nucleolar grade.

Predicting Meningioma Consistency on Preoperative Neuroimaging Studies.

This article provides an overview of the neuroimaging literature focused on preoperative prediction of meningioma consistency. A validated, noninvasive neuroimaging method to predict tumor consistency can provide valuable information regarding neurosurgical planning and patient counseling. Most of the neuroimaging literature indicates conventional MRI using T2-weighted imaging may be helpful to predict meningioma consistency; however, further rigorous validation is necessary. Much less is known about advanced MRI techniques, such as diffusion MRI, MR elastography (MRE), and MR spectroscopy. Of these methods, MRE and diffusion tensor imaging appear particularly promising.

Mapping of ApoE4 Related White Matter Damage using Diffusion MRI.

ApoliopoproteinE Ɛ4 (ApoE-Ɛ4) polymorphism is the most well known genetic risk factor for developing Alzheimers Disease. The exact mechanism through which ApoE 4 increases AD risk is not fully known, but may be related to decreased clearance and increased oligomerization of Aβ. By making measurements of white matter integrity via diffusion MR and correlating the metrics in a voxel-based statistical analysis with ApoE-Ɛ4 genotype (whilst controlling for vascular risk factor, gender, cognitive status and age) we are able to identify changes in white matter associated with carrying an ApoE Ɛ4 allele. We found potentially significant regions (Puncorrected < 0:05) near the hippocampus and the posterior cingulum that were independent of voxels that correlated with age or clinical dementia rating (CDR) status suggesting that ApoE may affect cognitive decline via a pathway in dependent of normal aging and acute insults that can be measured by CDR and Framingham Coronary Risk Score (FCRS).