Barry Daly

An anatomically comprehensive atlas of the adult human brain transcriptome

Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ∼900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography—the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.

CT and Clinical Features of Acute Diverticulitis in an Urban U.S. Population: Rising Frequency in Young, Obese Adults

OBJECTIVE On the basis of our experience in recent years, we hypothesized that acute diverticulitis occurs more frequently in young adult patients (age, < or = 50 years) now than previously recognized. We reviewed the CT findings, clinical features, and demographic data of a cohort of patients who presented with acute diverticulitis at an urban U.S. academic medical center. MATERIALS AND METHODS We used our hospital and radiology databases to identify 104 adult patients with both CT and clinical diagnoses of acute diverticulitis. Clinical parameters recorded included age, sex, ethnicity, in- or outpatient management, and therapy (medical treatment, percutaneous drainage, or surgery). CT studies were evaluated for the site of diverticulitis; associated complications; and the presence of abdominal obesity, as determined by measurement of sagittal abdominal diameter. RESULTS The study group was composed of 55 men and 49 women (age range, 22-88 years; mean age, 52.2 years; median age, 49.0 years). Fifty-six (53.8%) were 50 years old or younger, and 22 were 40 years old or younger. Forty-one complications were noted in 38 patients (36%). There was no significant age difference between the < or = 50 and > 50 years old age groups for hospital admission (90 patients, 86.5%), medical therapy (76, 73.1%), or surgery or percutaneous abscess drainage (28, 26.9%). Abdominal obesity measured by sagittal abdominal diameter was present in 48 (85.7%) and 37 (77%) of the < or = 50 and > 50 years old age groups, respectively. The mean sagittal abdominal diameter for patients < or = 50 years old (27.0 cm) was greater than that for patients > 50 years old (25.6 cm) (p = 0.05). CONCLUSION In this urban population, acute diverticulitis occurred more frequently in patients 20-50 years old than previously recognized. This group had significantly greater abdominal obesity than the older group. Severe disease requiring hospital admission, surgery, or percutaneous drainage (or both surgery and percutaneous drainage) was common in all age groups.

Clinical Predictors of Defibrillation Thresholds with an Active Pectoral Pulse Generator Lead System

HODGSON, D.M., et al.: Clinical Predictors of Defibrillation Thresholds with an Active Pectoral Pulse Generator Lead System. Active pectoral pulse generators are used routinely for initial ICD placement because they reduce DFTs and simplify the implantation procedure. Despite the common use of these systems, little is known regarding the clinical predictors of defibrillation efficacy with active pulse generator lead configurations. Such predictors would be helpful to identify patients likely to require higher output devices or more complicated implantations. This was a prospective evaluation of DFT using a uniform testing protocol in 102 consecutive patients with an active pectoral can and dual coil transvenous lead. For each patient, the DFT was measured with a step‐down protocol. In addition, 34 parameters were assessed including standard clinical echocardiographic and radiographic measures. Multivariate stepwise regression analysis was performed to identify independent predictors of the DFT. The mean DFT was 9.3 ± 4.6 J and 93% (95/102) of patients had a DFT ≤ 15 J. The QRS duration, interventricular septum thickness, left ventricular mass, and mass index were significant but weak (R < 0.3) univariate predictors of DFT. The left ventricular mass was the only independent predictor by multivariate analysis, but this parameter accounted for < 5% of the variability of DFT measured (adjusted R2= 0.047, P = 0.017). The authors concluded that an acceptable DFT (< 15 J) is observed in > 90% of patients with this dual coil and active pectoral can lead system. Clinical factors are of limited use for predicting DFTs and identifying those patients who will have high thresholds.

Pulmonary zygomycosis: CT appearance.

Objective We describe the CT appearance of pulmonary zygomycosis (mucormycosis), an opportunistic infection typically occurring in immunocompromised patients. Materials and Methods Eight patients with pulmonary zygomycosis imaged with CT were reviewed, seven at initial diagnosis and one with a subsequent complication. The appearance, number, and location of pulmonary lesions and the presence of pleural effusions and extrapulmonary involvement were assessed. Rim enhancement, air bronchograms, the halo sign, air crescent sign, cavitation, and central low attenuation suggesting necrosis were recorded. Results There were 14 nodules and 5 areas of mass-like or wedge-shaped consolidation. Pleural effusion was present in five patients, halo sign in three, central low attenuation in two, and cavitation in one. In the affected lobe 13 of 14 nodules and all consolidations were posterior. Of 19 lesions 16 (84%) were confined to the upper lobes, with 3 in the superior segment of a lower lobe. Endobronchial disease with lobar collapse was the only manifestation in one patient. Major complications were direct spinal invasion in one patient and multiple pulmonary artery pseudoaneurysms in another patient. Conclusion In the appropriate clinical circumstance, nodules or mass-like or wedge-shaped consolidation, especially posteriorly in the upper lobes of the lung, should suggest zygomycosis. Endobronchial zygomycosis is less common.

Comparison of whole-body post mortem 3D CT and autopsy evaluation in accidental blunt force traumatic death using the abbreviated injury scale classification

Although 3D CT imaging data are available on survivors of accidental blunt trauma, little similar data has been collected and classified on major injuries in victims of fatal injuries. This study compared the sensitivity of post mortem computed tomography (PMCT) with that of conventional autopsy for major trauma findings classified according to the trauma Abbreviated Injury Scale (AIS). Whole-body 3D PMCT imaging data and full autopsy findings were analyzed on 21 victims of accidental blunt force trauma death. All major injuries were classified on the AIS scale with ratings from 3 (serious) to 6 (unsurvivable). Agreement between sensitivity of autopsy and PMCT for major injuries was determined. A total of 195 major injuries were detected (mean per fatality, 9.3; range, 1-14). Skeletal injuries by AIS grade included 37 grade 3, 45 grade 4, 12 grade 5, and 2 grade 6 major findings. Soft tissue injuries included 10 grade 3, 68 grade 4, 16 grade 5, and 5 grade 6 major findings. Of these, PMCT detected 165 (88 skeletal, 77 soft tissue), and autopsy detected 127 (59 skeletal, 68 soft tissue). PMCT agreed with autopsy in 86% and 76% of skeletal and soft tissue injuries, respectively. PMCT detected an additional 37 skeletal and 31 soft tissue injuries that were not identified at autopsy. Autopsy detected 8 skeletal and 22 soft tissue injuries that were not detected by PMCT. PMCT was more sensitive for skeletal (P=0.05) and head and neck region injury (P=0.043) detection. PMCT showed a trend for greater sensitivity than autopsy, but this did not reach statistical significance (P=0.083). 3D PMCT detected significantly more skeletal injuries than autopsy and a similar number of soft tissue injuries to autopsy and promises to be a sensitive tool for detection and classification of skeletal injuries in fatal blunt force accidental trauma. Use of the AIS scale allows standardized categorization and quantification of injuries that contribute to death in such cases and allows more objective comparison between autopsy and PMCT.

Predicting Unresectability in Pancreatic Cancer Patients: The Additive Effects of CT and Endoscopic Ultrasound

BackgroundA standardized method for predicting unresectability in pancreatic cancer has not been defined. We propose a system using CT and endoscopic ultrasound (EUS) to assess patients for unresectable pancreatic cancers.MethodsRadiologic and surgical data from 101 patients who underwent exploration/resection for pancreatic cancer were reviewed. Chi-squares were used to identify five factors significantly correlated with unresectability, which were incorporated into a scoring system (one point for each factor).ResultsThe resectability rates were 84, 56, and 10% for patients with scores of 0, 1, and 2, respectively. All four patients with three risk factors for unresectability had unresectable tumors. The most accurate results were achieved in patients evaluated with both CT and EUS.DiscussionThis scoring system stratifies pancreatic cancer patients into three groups: (1) patients with a score of zero (likely to undergo successful resection), (2) patients with a score of one (likely to benefit from laparoscopic staging prior to attempting resection), and (3) patients with a score of two or higher (low probability of successful resection, who may be better served by neoadjuvant therapy).

Cytoablative therapy with combined resection and cryosurgery for limited bilobar hepatic colorectal metastases

BACKGROUND Cryosurgery can be employed in patients with unresectable hepatic metastases when the tumor size and the number of metastases are limited. However, local recurrence can result from incomplete ablation. We proposed a trial of complete cytoablation with a combined approach of cryosurgery and hepatic resection for patients with bilobar hepatic metastases. METHODS Seven patients underwent cryosurgery alone (CRYO). Seven additional patients underwent combined resection and cryosurgery (CRYO+RES) for bilobar metastases. RESULTS In the CRYO group, 5 of 7 patients had at least one centrally located tumor. All 5 of these patients had early recurrence at the site of ablation. In the CRYO+RES group complete ablation was achieved in 7 of 7. Two (28.6%) of these patients developed local recurrence. CONCLUSION Cytoablation of hepatic metastases can be safely achieved with combined hepatic resection and cryosurgery in selected patients. Long-term survival data are necessary before advocating widespread application of this approach.

Hepatic Gas: Widening Spectrum of Causes Detected at CT and US in the Interventional Era

The spectrum of causes of hepatic gas detected at computed tomography (CT) and ultrasonography (US) is widening. There are many iatrogenic and noniatrogenic causes of hepatic parenchymal, biliary, hepatic venous, and portal venous gas. Hepatic gas may be an indicator of serious acute disease (infarct, infection, abscess, bowel inflammation, or trauma). In other clinical scenarios, it may be an expected finding related to therapeutic interventions (such as surgery; hepatic artery embolization for a tumor or for active bleeding in acute trauma cases; percutaneous tumor ablation performed with radiofrequency, cryotherapy, laser photocoagulation, or ethanol). In some cases, hepatic gas is an incidental finding of no clinical significance. Familiarity with the expanding list of newer intervention-related causes of hepatic gas detected at CT and US, knowledge of the patients clinical history, and a careful search for associated clues on images are all factors that may allow the radiologist to better determine the clinical relevance of this finding.

End stage renal transplant failure : Allograft appearances on CT

INTRODUCTION Failed renal allografts often are left in situ in patients who revert to chronic dialysis therapy or who undergo retransplantation. These patients may be investigated with computed tomography (CT) imaging for allograft-related or other abdominopelvic disease. This study describes the appearances of failed renal transplants on CT. METHODS A retrospective study was made of the clinical records and CT findings on 25 studies in 14 patients, 5-156 months (average, 44 months) following allograft failure. CT studies were reviewed for allograft position, size, shape, attenuation value, calcification, cyst formation, related abdominopelvic findings and the presence of other allografts. Correlation was made with clinical findings in all patients and with pathological findings in six. RESULTS Global shrinkage was noted in eight failed allografts, all of which were asymptomatic. Enlargement of two failed allografts was due to symptomatic acute infarction of the allograft in one patient and subacute haemorrhagic infarction simulating a tumour mass in another. CT attenuation values in individual allografts varied markedly due to fatty replacement, hydronephrosis, haemorrhage or dense calcification. Both a failed longstanding and a functioning more recently placed renal allograft were present in seven patients, four of whom had acute complications related to the more recently transplanted kidney. Two of six calcified allografts were mistaken for opacified bowel on CT. CONCLUSION A wide spectrum in size, shape and attenuation values may be detected in failed renal allografts by CT. These organs may be the site of acute disease despite their lack of physiological function or may be diagnostically confusing findings in patients with acute disease related to more recently transplanted organs.

Interventional Procedures in Whole Organ and Islet Cell Pancreas Transplantation

Pancreas organ transplantation has been a therapeutic option for the treatment of diabetes mellitus for over a decade. More recently, percutaneous injection of isolated pancreas islet cells via the portal vein has been developed as an exciting minimally invasive alternative procedure to whole organ transplantation, and one where the interventional radiologist may play a major role. This chapter reviews the role of image guided intervention in the whole organ pancreas transplant and describes the evolving technique of percutaneous islet cell transplantation.