Similar clinical and neuroimaging features in monozygotic twin pair with mutation in progranulin.

OBJECTIVE: To report the phenotypic characterization of monozygotic twins with mutations encoding progranulin (PGRN). METHODS: We studied a twin pair with an exon 4 gene deletion in the PGRN gene. Both twins had clinical and neuropsychological examinations as well as structural MRI and fluorodeoxyglucose PET (FDG-PET) scans. PGRN gene sequencing was performed followed by progranulin ELISA in plasma. RESULTS: Both twins manifested symptoms within 3 years of each other, with early behavioral, language, dysexecutive, and memory problems. MRI and FDG-PET imaging demonstrated a strikingly similar topography of findings with clear left hemisphere predominance. Serum progranulin levels in both were well below those from a normal population sample. CONCLUSIONS: Compared with the heterogeneity seen in many families with PGRN mutations, these monozygotic twins demonstrated strong clinical, neuroimaging, and serum progranulin level similarities, demonstrating the importance of shared genetic profiles beyond environmental influences in the symptomatic expression of the disease.

Fluorodeoxyglucose-positron-emission tomography imaging of head and neck squamous cell cancer.

The hybrid technique of PET/CT has significantly impacted the imaging and management of HNSCC since its introduction in 2001 and has become the technique of choice for imaging of this cancer. Diagnostic FDG-PET/CT is useful for identification of an unknown primary tumor, delineation of extent of primary tumor, detection of regional lymph node involvement even in a normal-sized node, detection of distant metastases and occasional synchronous primary tumor, assessment of therapy response, and long-term surveillance for recurrence and metastases. The role of PET/CT is evolving in radiation therapy planning. Combined diagnostic PET/CT provides the best anatomic and metabolic in vivo information for the comprehensive management of HNSCC.

The Geneva prognostic score and mortality in patients diagnosed with pulmonary embolism by CT pulmonary angiogram.

This study prospectively evaluates whether a previously established adverse outcome score (the Geneva prognostic score) predicts 3 and 12-month overall mortality among the patients diagnosed with pulmonary embolism (PE) by a CT pulmonary angiogram (CTPA). Five hundred twenty-three consecutive patients who had CTPA for suspected PE were recruited prospectively from March 2003 to October 2004. The Geneva prognostic score was calculated for all patients. Twelve-month follow up was completed in all patients in December 2005. There were 105 patients diagnosed with PE. The mean score was 2.71 (standard deviation (SD) 1.25) for those patients who had died (n = 7) and 1.14 (SD 1.19) for those patients who were alive (n = 98) at 3-month follow up (P < 0.001). The mean scores were 2.69 (SD 0.95) for those who had died (n = 13) and 1.04 (SD 1.15) for those patients who were alive (n = 92) at 12-month follow up (P < 0.001). At 3-month follow up, among the 88 patients with a score of 2 or less, three patients (3.4%) died and among 17 patients with a score of greater than 2, four patients (23.5%) died (P = 0.01). At 12-month follow up, five patients (5.7%) with a score of 2 or less died and eight patients (47.1%) with a score of three or more died (P < 0.0001). The Geneva prognostic score stratifies patients with low and high risk for overall mortality at 3 and 12 months among patients diagnosed with PE by CTPA.

18F-fluoro-2-deoxy-D-glucose positron emission tomography and positron emission tomography/computed tomography imaging of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is the most common primary pleural tumor and its incidence is rising. Its diagnosis, staging and response assessment are challenging for imaging. Integrated positron emission tomography (PET)/CT increases the accuracy of overall staging in patients with mesothelioma and improves the selection of patients for curative surgical resection. It is particularly useful in identifying occult distant metastases. It may be used to predict prognosis and to assess the metabolic response to therapy.

An algorithm for predicting nonorgan confined prostate cancer using the results obtained from sextant core biopsies with prostate specific antigen level.

PURPOSE: We determined the enhanced ability to predict nonorgan confined prostate cancer using several histopathological and quantitative nuclear imaging parameters combined with serum prostate specific antigen (PSA). MATERIALS AND METHODS: Several independent pathological and quantitative image analysis variables obtained from sextant biopsy specimens, as well as preoperative PSA were used. The study population included 210 patients with pathologically staged disease (192 with PSA). All variables were examined by univariate and multivariate logistic regression analyses to assess ability to predict disease organ confinement status. RESULTS: Univariate logistic regression analysis demonstrated that, in decreasing order, quantitative nuclear grade, preoperative PSA, total percent tumor involvement, number of positive sextant cores, preoperative Gleason score and involvement of more than 5% of a base and/or apex biopsy were significant (p < or = 0.006) for prediction of disease organ confinement status. Backward stepwise logistic regression was applied to these univariately significant variables, including deoxyribonucleic acid ploidy, to calculate a multivariate model for prediction of disease organ confinement status. This algorithm had a sensitivity of 85.7%, specificity 71.3%, positive predictive value 72.9%, negative predictive value 84.7% and area under the receiver operating characteristic curve 85.9%. CONCLUSIONS: Information from pathological study of sextant prostate biopsies, preoperative PSA blood test and a new image analysis variable termed quantitative nuclear grade can be combined to create a multivariate algorithm that can predict more accurately nonorgan confined prostate cancer compared to previously reported methods.

First pass Tc-99m MIBI ventriculography in the assessment of left ventricular diastolic function. A comparison with Doppler echocardiography.

Tc-99m MIBI is used for myocardial imaging and first-pass studies. However, little is known about its utility in the assessment of left ventricular diastolic function. The authors retrospectively compared first pass studies of Tc-99m MIBI at rest with Doppler flow velocity measurements to assess left ventricular diastolic performance. Thirty-nine patients who had both studies performed within 48 hours of each other were evaluated. Three indices of diastolic function were measured by first pass Tc-99m MIBI ventriculography and Doppler echocardiography: 1) Time to peak early diastolic velocity; 2) normalized peak filling rate; and 3) half filling fraction. The results demonstrated a correlation of 0.82 (P < 0.001), 0.82 (P < 0.001), and 0.53 (P = 0.001) for the above indices, respectively. This study indicates that the indices of left ventricular diastolic function by first pass Tc-99m MIBI compare favorably with those derived from Doppler flow velocity measurements in which the diagnostic value has been previously established. Both methods accurately reflect diastolic flow and may facilitate clinical evaluation of diastolic function.

Diagnostic criteria for assessing obstruction in the newborn with unilateral hydronephrosis using the renal growth-renal function chart.

Previous studies in newborns with unilateral hydronephrosis demonstrated that the contralateral normal kidney can rapidly compensate for changes in function in the hydronephrotic kidney by increasing or decreasing its growth rate. To formulate diagnostic criteria for assessing obstruction using compensatory growth responses we developed a renal growth-renal function chart that graphically describes the normal renal growth rate in young children. This chart allows changes in function in the hydronephrotic kidney to be graphically compared to changes in length of the contralateral normal kidney. The renal growth-renal function chart was used to assess obstruction in 47 neonates with primary unilateral hydronephrosis. Four reproducible, clinically relevant diagnostic patterns of differential function and growth were identified: 1) obstruction, 2) corrected obstruction, 3) no obstruction with good differential function (greater than 40%) and 4) no obstruction but poor differential function (less than 40%). The renal growth-renal function chart helped to identify and exclude obstruction, and provided welcome reassurance that nonobstructive hydronephrosis was not harming the kidney. It appears to have potential for improving diagnostic accuracy in newborns with hydronephrosis.

Sextant prostate biopsies. A histopathologic correlation with radical prostatectomy specimens.

BACKGROUND: Among patients with clinically localized prostate cancer, preoperative prediction of tumor volume and pathologic stage has been unreliable. This study examines the application of transrectal ultrasound-guided sextant biopsies to predict the extent of disease. METHODS: One hundred and two patients with clinically resectable prostate cancer were evaluated by systematic sextant biopsies. Radical prostatectomy specimens were embedded totally as whole mounts, tumor areas were outlined, and volume was measured using a digital scanner. The number of positive sextant biopsies was compared with age, race, preoperative prostate specific antigen (PSA), PSA density, DNA ploidy, pathologic stage, capsular and seminal vesicle involvement, prostate and tumor volume, and Gleason score. Stepwise logistic regression was used to determine if pathologic stage or tumor size could be predicted by these parameters. RESULTS: The number of positive sextant biopsies correlated with traditional prognostic indicators. When patients with three or fewer positive biopsies were compared with those with four or more positive sextant biopsies, significant differences were identified relative to preoperative PSA (P < 0.001), tumor volume (P < 0.001), pathologic stage (P < 0.001), Gleason score (P < 0.001), seminal vesicle involvement (P < 0.001), and capsular penetration (P < 0.001). There were no significant differences based on age, race, DNA ploidy, and overall prostate volume. Logistic regression showed that patients with four or more positive sextant biopsies and high Gleason score had a greater likelihood of pT3 classification. Likewise, the probabilities of a tumor volume less than 0.5 ml could be predicted by the number of positive sextant biopsies and PSA alone. The number of positive sextant biopsies was the only factor that could predict a tumor volume greater than 4.0 ml. CONCLUSION: The number of positive sextant biopsies appears to be an important prognostic indicator of pathologic (pT) classification and tumor volume. This information is valuable in selecting the treatment strategy for patients with prostate cancer.

Gardner's syndrome. Case report and discussion of the manifestations of the disorder.

Extracolonic manifestations of Gardner's syndrome are common and may precede the detection of colonic polyps. Tc-MDP bone scintigraphy performed on a patient with Gardner's syndrome demonstrated intense uptake of radiotracer within the maxilla and mandible as a result of the dental anomalies associated with this disorder. Nuclear scintigraphy has a role in the imaging of these patients for skeletal anomalies, the detection of thyroid carcinoma, and for skeletal metastases when colon carcinoma is detected.

The assessment of obstruction in the newborn with unilateral hydronephrosis by measuring the size of the opposite kidney.

We measured the size of the normal kidney opposite a unilateral hydronephrotic kidney in infants to determine if compensatory changes occurred and could be used as a diagnostic test for defining or excluding obstruction. Comparison of subgroups of neonates with unilateral hydronephrosis or multicystic renal dysplasia to normal controls demonstrated that compensatory changes do occur in the normal kidney. Normal kidneys opposite obstructed hydronephrotic kidneys requiring surgery became larger than normal for age. Normal kidneys opposite nonobstructed poorly functioning hydronephrotic kidneys whose function rapidly improved were smaller than normal for age. These changes in renal growth by the normal newborn kidney reflect renal counterbalance, which is exaggerated in this age group and which may be used to corroborate rapid changes in renal function caused by the presence or absence of obstruction. By plotting serial measurements of normal renal length on a renal growth chart, the diagnosis of obstruction in newborn hydronephrosis can be facilitated and the clinical management of the patient improved.

Noncompartmental and compartmental modeling of the kinetics of carbon-11 labeled pyrilamine in the human brain.

The kinetic pattern of a 11C-labeled histamine H1 receptor antagonist, [11C]pyrilamine, was investigated in the human brain by factor analysis of dynamic PET studies. Tissue time activity curves were also processed by compartment model curve fitting preceded by deconvolution analysis. Factor analysis revealed two statistically significant and physiologically meaningful kinetic patterns: one for specific and another for nonspecific binding of the radioligand. From these two factors a compartment model containing two tissue compartments (one for specific binding and another for nonspecific binding and free ligand) was constructed. The two-compartment model was also supported by the impulse response function, which was obtained by deconvolution and showed two components. The factor image constructed from factor two demonstrated a distribution pattern characteristic for brain regions rich (frontal, parietal, and temporal lobes) or poor (occipital lobe and cerebellum) in H1 receptors. Blockade of H1 receptors with unlabeled pyrilamine, diphenhydramine, or hydroxyzine caused a significant reduction of this factor. Blockade produced no significant changes in factor one representing nonspecific binding. We conclude that the kinetics of [11C]pyrilamine in the brain can be described by two tissue compartments, one related to the distribution of the H1 receptors. Factor analysis of dynamic studies can be used to locally separate these two compartments, for identification of regions rich and poor in H1 receptors and for noninvasive quantitative investigation of the effects of H1 receptor blockers such as pyrilamine, diphenhydramine, or hydroxyzine.

Extraosseous Tc-99m MDP uptake: a pathophysiologic approach.

Scintigraphy with technetium-99m methylene diphosphonate (MDP) delineates a wide spectrum of nonosseous disorders. Neoplastic, hormonal, inflammatory, ischemic, traumatic, excretory, and artifactual entities demonstrate abnormal soft-tissue uptake of Tc-99m MDP. Mechanisms leading to increased extraosseous Tc-99m MDP uptake include extracellular fluid expansion, enhanced regional vascularity and permeability, and elevated tissue calcium concentration. The composition of the calcium deposition and the presence of other metallic ions (eg, iron and magnesium) are important. Soft-tissue Tc-99m MDP uptake is seen in benign (tumoral calcinosis, myositis ossificans) and malignant (sarcomas, adenocarcinomas, metastases) neoplastic entities. Hormonal disturbances in calcium metabolism, especially in hyperparathyroidism, can lead to metastatic calcification, visualized with Tc-99m MDP scintigraphy. Tissue damage from inflammation, infection, or physical trauma results in localized hyperemia, edema, or calcium (and hemosiderin) deposition based on their pathophysiologic characteristics. Urinary tract obstruction, anomalies, or dysfunction are demonstrated by Tc-99m MDP imaging. Common artifacts are related to faulty radiopharmaceutical preparation, Tc-99m MDP administration, and imaging technique. Recognition of these modes of extraskeletal Tc-99m MDP uptake can enhance the diagnostic value of bone scintigraphy.

Transient diaphyseal tibial Tc-99m MDP uptake and bone marrow edema in acute rheumatic fever.

The authors describe a patient with acute rheumatic fever and polyarthritis in whom scintigraphy unexpectedly identified Tc-99m MDP uptake in the diaphyses of both tibiae. A dramatic rise in antistreptolysin-O titer and rapid resolution of tibial abnormalities paralleled marked articular improvement. Magnetic resonance imaging demonstrated a pattern consistent with marrow edema in the area of abnormal Tc-99m MDP accumulation. This finding has not been previously described in acute rheumatic fever, and it was suspected that the changes in the tibiae resulted from subclinical diaphyseal hyperemia from the inflammatory process observed in the contiguous joints.

Pacemaker-induced friction rub and apical thrill.

A patient with acute myocardial infarction developed a loud systolic sound and apical thrill. Doppler ultrasound excluded interventricular septal rupture and significant mitral or tricuspid regurgitation. Auscultatory abnormalities disappeared after removal of a temporary pacing electrode, suggesting that the friction it created with intracardiac structures was responsible for these findings.

Prolonged clearance is the primary abnormal reflux parameter in patients with progressive systemic sclerosis and esophagitis.

The purpose of this study is to determine if frequent reflux events from an incompetent LES or poor clearance from decreased peristalsis is the predominant abnormality in PSS patients with severe reflux esophagitis. Seven patients with both classic manometric findings of PSS and endoscopic findings of esophageal ulcerations and/or Barrett's esophagus were compared to nine patients with similar endoscopic findings but with no evidence of a connective tissue disorder. All patients underwent simultaneous intraesophageal pH monitoring and scintigraphy for a total of 40 min after a radiolabeled meal. Four of the PSS patients and all the non-PSS patients had simultaneous manometry. We found that PSS patients had significantly fewer reflux events (P less than 0.01), but the reflux events had significantly longer duration (P less than 0.01) compared to patients with similar severity of esophagitis and no connective tissue disease. We conclude that decreased smooth muscle peristalsis appears to be the primary contributor to acid exposure and esophageal injury in PSS.

Small cell lung cancer: staging with MR imaging.

Small cell lung cancer is an aggressive neoplasm; metastases are detected in two-thirds of patients at diagnosis with use of conventional staging, which includes bilateral bone marrow biopsy, bone scintigraphy, and computed tomography (CT) of the head and abdomen. In 25 patients, small cell lung cancer was staged prospectively with both conventional staging and a magnetic resonance (MR) imaging protocol that included 1.5-T MR imaging of the pelvis, abdomen, spine, and brain. According to conventional staging, 14 patients had extensive disease and 11 patients had limited disease; according to staging with MR, 19 patients had extensive disease and six had limited disease. All metastatic disease sites seen with conventional staging were identified on MR images. MR images showed additional metastatic involvement in bone (four patients) and liver (three patients) not detected at conventional staging. A low-attenuation hepatic lesion on a CT scan was identified as a hemangioma on MR images. These preliminary data suggest that small cell lung cancer may be accurately staged with use of a single MR imaging study.

Management of urinary incontinence by bladder tube urethral lengthening and submucosal reimplantation.

We reviewed the first 25 urethral lengthening and reimplantation procedures done at our institution in 24 patients. All patients had failed to achieve dryness on medical or surgical therapy for total urinary incontinence. A total of 32 patients had neurogenic incontinence. The patients were followed for 1.5 to 7 years. Late complications included catheterization difficulties, vesicoureteral reflux, febrile urinary tract infection, calculi and peritonitis. Reoperations were required in 19 patients primarily because of our initial failure to recognize the necessity of providing a low pressure, high capacity reservoir. The reoperation rate on the continence mechanism was low. Of 24 patients 20 are continent and require no pads or diapers.