Biomedical subjects

Elkan F Halpern

Publications and source records attributed to Elkan F Halpern.

At least 19 recordsLinked to original sources

PubMed2006

Mullerian Inhibiting Substance enhances subclinical doses of chemotherapeutic agents to inhibit human and mouse ovarian cancer.

Mullerian Inhibiting Substance (MIS), a biological modifier that causes regression of Mullerian ducts in male embryos, is effective as a single agent in vitro and in vivo against human and mouse ovarian cancer cell lines expressing MIS type II receptor; however, little is known about how recombinant human MIS (rhMIS), now being scaled for preclinical trials, could be used in combination with cytotoxic or targeted chemotherapeutic agents. Mouse serous and endometrioid ovarian carcinoma cell lines were tested in vitro against rhMIS alone and with doxorubicin, paclitaxel, or cisplatin as agents in clinical use. Because MIS releases FK506 binding protein (FKBP12), which activates the mammalian target of rapamycin (mTOR) downstream of Akt, rhMIS and rapamycin combinations were tested. MIS increases p16 protein levels, and 5'-Aza-2'-deoxycytidine (AzadC) induces p16 mRNA; therefore, they were used in combination in vitro and in vivo with a human ovarian cancer cell line. A paclitaxel-resistant human ovarian cancer cell line and its parental line both respond to rhMIS in vitro. Additivity, synergy, or competition was observed with MIS and rapamycin, AzadC, doxorubicin, cisplatin, and paclitaxel, suggesting that MIS in combination with selective targeted therapies might achieve greater activity against ovarian cancer than the use of each individual agent alone. These assays and statistical analyses could be useful in selecting rhMIS and chemotherapeutic agent combinations that enhance clinical efficacy and reduce toxicity.

Animals↗

PubMed2006

Uterine malignant mixed mullerian tumors should not be included in studies of endometrial carcinoma.

OBJECTIVE: Uterine mixed malignant mullerian tumors (MMMT) have traditionally been excluded from clinical trials of endometrial cancer because of a belief that they are more correctly included in the sarcoma category. Recently, investigators have suggested that uterine MMMTs are actually dedifferentiated epithelial tumors and should be treated as such. The current study was undertaken to compare outcomes, stage for stage, of uterine MMMT with poor prognosis endometrial adenocarcinomas. METHODS: Cases of MMMT from 1996 to 2004 were identified from the Tumor Registry after IRB consent was obtained. Retrospective chart review was performed. Cases were matched by age, stage, performance status, and surgical procedure to controls consisting of grade 3 endometrioid, papillary serous, and clear cell endometrial carcinomas from the same time period. Overall survival was compared using the Log-Rank test. RESULTS: 68 patients with MMMT were identified. 23 were excluded due to incomplete records. Patients with MMMT ranged in age from 51 to 95 years (mean 75.3 years). Approximately half of the patients (53%) had stage III or IV disease. Of the controls, 31 (69%) had grade 3 endometrioid, 11 (24%) papillary serous, and 3 (7%) clear cell carcinoma. Median overall survival for all patients with MMMT was significantly shorter than for controls, 18 months (range 0.5-72) versus 36 months (range 0.5-123) (P = 0.02). Patients with early stage disease (stage I or II) had shorter median survival than controls, 26 months (range 3-7) vs. 95 months (range 4-123) (P = 0.003). There was no difference in median survival when comparing advanced disease (stage III or IV) to matched controls, 15 months (range 0.5-70) vs. 19 months (range 0.5-100) (P = NS). CONCLUSIONS: Patients with uterine MMMT have a poorer prognosis than those patients with high grade epithelial tumors, especially for those with early stage disease. Given the discrepancy in survival, these patients should not be included in studies of endometrial carcinoma. Further investigations are necessary to identify factors to improve survival of these patients.

Carcinoma, Endometrioid↗

PubMed2006

Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury.

AIMS: Currently available non-invasive imaging methods frequently fail to detect alterations in left ventricular (LV) function despite histological evidence of injury. Tissue Doppler imaging (TDI) can detect subtle LV dysfunction. The aim of this study was to investigate whether TDI indices can predict LV systolic dysfunction and mortality following exposure to doxorubicin (DOX) in mice. METHODS AND RESULTS: TDI-derived peak endocardial systolic velocity (V(ENDO)) and strain rate (SR), as well as M-mode and two-dimensional indices of LV systolic function, were measured serially in mice after receiving DOX as a single dose (20 mg/kg). Haemodynamic measurements were obtained invasively before and at 1, 2, 4, and 5 days after the single DOX dose. Cardiac apoptosis was measured before and at 1 day after DOX. V(ENDO) and SR decreased after 1 and 2 days, respectively, whereas changes in fractional shortening (FS) and LV ejection fraction (LVEF) were not detected before 5 days. The reduction in both V(ENDO) and SR correlated with the decrease in dP/dt(MAX), and the change in V(ENDO) correlated with the early increase in cardiac cell apoptosis. In a subsequent experiment, DOX was administered at 4 mg/kg/week for 5 weeks, and LV function was followed serially for 16 weeks. In this chronic experiment, TDI indices decreased before FS and LVEF, correlated with late LV dysfunction, and predicted DOX-induced mortality. CONCLUSION: In a murine model of DOX-induced cardiac injury, TDI detects LV dysfunction prior to alterations in conventional echocardiographic indices and predicts mortality. This study suggests that TDI may be a reliable tool to detect early subtle changes in DOX-induced cardiac dysfunction.

Animals↗

PubMed2006

Iloprost attenuates doxorubicin-induced cardiac injury in a murine model without compromising tumour suppression.

AIMS: The use of doxorubicin (DOX) as a chemotherapeutic agent is limited by cardiac injury. Iloprost, a stable synthetic analogue of prostacyclin, has previously been shown to protect against DOX-induced cardiomyocyte injury in vitro. Here, we addressed whether iloprost is cardioprotective in vivo and whether it compromises the anti-tumour efficacy of DOX. METHODS AND RESULTS: Lewis Lung Carcinoma cells were implanted subcutaneously in the flank of C57BL/6 mice. DOX treatment was commenced from when tumours became visible. Iloprost was administered from prior to DOX treatment until sacrifice. Echocardiography and invasive haemodynamic measurements were performed immediately before sacrifice. As expected, DOX induced cardiac cell apoptosis and cardiac dysfunction, both of which were attenuated by iloprost. Also, iloprost alone had no effect on tumor growth and indeed, did not alter the DOX-induced suppression of this growth. CONCLUSION: In a murine model, iloprost attenuated the acute cardiac injury and dysfunction induced by DOX therapy without compromising its chemotherapeutic effect.

Animals↗

PubMed2006

Persistent and reversible cardiac dysfunction among amateur marathon runners.

AIMS: Transient systolic and diastolic abnormalities in ventricular function have previously been documented during endurance sports. However, these described alterations may be limited by the techniques applied. We sought, using less load-dependent methods, to characterize both the extent and the chronology of the cardiac changes associated with endurance events. METHODS AND RESULTS: Transthoracic echocardiography (TTE) was performed prior to, immediately after, and approximately 1 month after completion of the 2003 Boston Marathon in 20 amateur athletes. TTE included two-dimensional, spectral and tissue Doppler (TD) and flow propagation velocity (V(p)). After completion of the marathon, global measures of left ventricular (LV) systolic function were unchanged (EF 59 +/- 6 vs. 61 +/- 4% post, P = 0.14), whereas TD-derived measures of LV systolic function [septal strain -23 +/- 5 vs. -17 +/- 4%, P = 0.007; septal strain rate (SR) -1.5 +/- 0.3 vs. -1.1+/- 0.2 s(-1), P = 0.007] and right ventricular (RV) systolic function (RV apical strain -33 +/- 4 vs. -27 +/- 5%, P = 0.001; RV apical SR -2.4 +/- 0.7 vs. -1.8 +/- 0.5, P = 0.002) were reduced. Significant changes in transmitral velocity (E/A ratio 2.0 +/- 0.5 vs.1.3 +/- 0.3, P = 0.005) and TD indices of LV and RV diastolic function (E(a) septal 9.5 +/- 1.8 vs. 8.1 +/- 1.2 cm/s post-marathon, P = 0.01) were also observed, indicating an inherent alteration in LV relaxation. Although all indices of LV and RV systolic function had returned to normal on follow-up, there were persistent diastolic abnormalities (RV E(a), 11.5 +/- 1.5 cm/s pre-marathon vs. 10.0 +/- 1.6 cm/s follow-up, P = 0.01). CONCLUSION: Marathon running leads to transient systolic and more persistent diastolic dysfunction of both the LV and the RV.

Adult↗

PubMed2006

Accuracy of transmission CT and FDG-PET in the detection of small pulmonary nodules with integrated PET/CT.

PURPOSE: The purpose of this study was to determine the accuracy of detection of small pulmonary nodules on quiet breathing attenuation correction CT (CTAC) and FDG-PET when performing integrated PET/CT, as compared with a diagnostic inspiratory CT scan acquired in the same imaging session. METHODS: PET/CT scans of 107 patients with a history of carcinoma (54 male and 53 female, mean age 57.3 years) were analyzed. All patients received an integrated PET/CT scan including a CTAC acquired during quiet respiration and a contrast-enhanced CT acquired during inspiration in the same session. Breathing CTAC scans were reviewed by two thoracic radiologists for the presence of pulmonary nodules. FDG-PET scans were reviewed to determine accuracy of nodule detection. Diagnostic CT was used as the gold standard to confirm or refute the presence of nodules. RESULTS: On the CTAC scans 200 nodules were detected, of which 183 were true positive (TP) and 17, false positive. There were 109 false negatives (FN). Overall, 51 (48%) patients had a false interpretation, including 19 in whom CT was interpreted as normal for lung nodules. The average size of the nodules missed was 3.8+/-2 mm (range 2-12 mm). None of the nodules missed on the CTAC scans were detected by PET. In the right lung there were 20 TP, 42 true negative (TN), 11 FP, and 34 FN interpretations with a sensitivity in nodule detection of 37% (CI 24-51%) and a specificity of 79% (CI 66-89%). In the left lungs there were 16 TP, 65 TN, 3 FP, and 23 FN interpretations, with a sensitivity of 41% (CI 26-58%) and a specificity of 96% (CI 88-99%). CONCLUSION: The detection of small pulmonary nodules by breathing CTAC and FDG-PET is relatively poor. Therefore an additional diagnostic thoracic CT scan obtained during suspended inspiration is recommended for thorough evaluation of those patients in whom detection of pulmonary metastases is necessary for management.

Adolescent↗

PubMed2006

Recombinant human Mullerian inhibiting substance inhibits long-term growth of MIS type II receptor-directed transgenic mouse ovarian cancers in vivo.

PURPOSE: Mullerian inhibiting substance (MIS) is a glycoprotein hormone that causes Mullerian duct regression in male embryos. In short-term experiments, recombinant human MIS (rhMIS) inhibits xenotransplanted human ovarian cancer cell lines that are thought to be of Mullerian origin. Because this highly lethal cancer has a high recurrence rate after conventional chemotherapy, new treatments are warranted. We examined whether rhMIS as a novel, nontoxic, naturally occurring growth inhibitor can be an effective anticancer drug in long-term studies in vivo against allograft tumors that recapitulate human ovarian carcinoma. EXPERIMENTAL DESIGN: Mouse ovarian carcinoma (MOVCAR) cell lines expressing the early region of the SV40 virus, including the large and small T-antigen genes under transcriptional control of a portion of the murine MIS receptor type II (MISRII) gene promoter, were derived from TgMISIIR-TAg transgenic mice. rhMIS was tested against MOVCAR cells in growth inhibition assays in vitro, and in vivo in 6-week-old female nude mice. Tumor growth in animals was measured at weekly intervals for up to 20 weeks. RESULTS: MOVCAR cells and tumors express MISRII by Western blot, immunohistochemical, and Northern blot analyses. rhMIS significantly inhibited MOVCAR cell growth in vitro and in vivo in three separate long-term allotransplantation experiments. CONCLUSIONS: Because rhMIS is an effective anticancer agent in in vitro and in long-term in vivo preclinical experiments against MISRII-positive tumors, we predict that rhMIS can be used safely and effectively to treat human ovarian malignancies.

Animals↗

PubMed2006

A rational approach to the stool ova and parasite examination.

BACKGROUND: Examination of multiple stool specimens per patient to rule out parasitic infection continues to be recommended in the literature. Attractive alternatives have been proposed, such as examination of a single specimen, but data to support their use have been inconclusive. METHODS: We reviewed the results of comprehensive stool ova and parasite examinations performed during a 1-year period to determine the incremental value of examining >1 specimen. Next, we implemented rejection criteria, allowing analysis of only a single specimen in most cases, and studied the impact of the change by reviewing data from a subsequent year. RESULTS: Prior to implementation of rejection criteria, 91% of parasites were detected in the first specimen submitted, although many clinical evaluations (72%) involved the submission of only 1 stool specimen. When at least 3 specimens were submitted, the sensitivity of examining the first in the series was 72%. Even the latter sensitivity provides negative predictive values of approximately 98%, approximately 97%, approximately 95%, or approximately 93% when the prevalence of parasites among those tested is 5%, 10%, 15%, or 20%, respectively. Examination of additional specimens after examination of the first specimen that yielded a positive finding revealed previously undetected parasites in only 10% of cases. After the application of rejection criteria, the parasite detection rate did not change significantly. CONCLUSIONS: Comprehensive examination of a single stool specimen is sufficient for most patients, when the prevalence of infection among the tested population is up to 20%. Rational use of the stool ova and parasite examination relies on communication between clinician and laboratory, and retention of deferred specimens in case examination of additional specimens is clinically warranted.

Animals↗

PubMed2006

Myocardial adaptation to short-term high-intensity exercise in highly trained athletes.

We aimed to clarify the myocardial adaptation to short-term high-intensity exercise among trained athletes. We screened 17 participants in the 2004 World Indoor Rowing Championships before and after a 2000-m sprint. Echocardiography included standard measurements and tissue Doppler-derived strain (epsilon), strain rate, and 2-dimensionally derived speckle-tracking imaging for left ventricular (LV) torsion. LV volumes and ejection fraction were unchanged after exercise. There was a reduction in early and an increase in late diastolic filling velocities and a decrease in the flow propagation velocity. Annular systolic velocities, slope of the systolic acceleration, septal and lateral epsilon, and speckle tracking-derived torsion were increased. The increased LV torsion was a result of increased basal and apical rotation. Right ventricular apical epsilon decreased. In conclusion, maximal intensity short-duration exercise was associated with attenuation of LV diastolic function, augmentation of LV systolic function, and a reduction in apical right ventricular contractility.

Adaptation, Physiological↗

PubMed2006

Adrenal lesions: characterization with fused PET/CT image in patients with proved or suspected malignancy--initial experience.

PURPOSE: To retrospectively evaluate the accuracy of the fused positron emission tomographic (PET)/computed tomographic (CT) image for characterization of adrenal lesions in patients who have proved malignancy or are suspected of having malignancy. MATERIALS AND METHODS: Institutional review board approval was received for this retrospective HIPAA-compliant study, and informed consent was waived. Forty-one adrenal lesions in 38 patients (21 men, 17 women; mean age, 66 years; range, 37-86 years) were evaluated with PET/CT. Of the 41 lesions, nine were assumed to be malignant with documentation of enlargement (n = 8) or reduction in size in response to treatment (n = 1), and 32 were assumed to be benign with documentation of stability for 6 months (n = 31) or with confirmation with biopsy results (n = 1). The PET examination findings were positive when adrenal lesion maximum standardized uptake values (SUVs) exceeded hepatic maximum SUVs. CT contrast medium washout analysis was used to further characterize two lesions with PET findings positive for malignancy. The t test was used to assess significant (P < .05) differences between fluorine 18 fluorodeoxyglucose (FDG) uptake of benign lesions and that of malignant lesions. RESULTS: At PET/CT, findings for all malignant lesions were positive (mean adrenal lesion-liver activity ratio, 4.04; range, 1.53-17.08). Of the 32 benign lesions, most (30 of 32) had activity less than that of the liver (mean ratio, 0.66; range, 0.22-0.94). PET/CT demonstrated sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 93.8%, 81.8%, 100%, and 95.1%, respectively. Incorporating contrast material-enhanced CT with delayed imaging increased specificity to 100% because two lesions with PET findings positive for malignancy were characterized as benign. There was a significant difference between maximum SUV (P < .05) and the ratio of adrenal lesion-liver FDG activity (P < .001) in benign versus malignant adrenal lesions. CONCLUSION: PET/CT provides a powerful combination of functional and attenuation information for adrenal lesion characterization. All malignant lesions were detected at PET/CT, with no false-negative results.

Adrenal Gland Neoplasms↗

PubMed2006

Long-term risk of false-positive screening results and subsequent biopsy as a function of mammography use.

PURPOSE: To retrospectively determine the long-term risk of false-positive mammographic assessments and to evaluate the effect of screening regularity on the risk of false-positive events. MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was waived. Retrospective analysis was performed for the occurrence of false-positive assessments among 83,511 women who underwent 314,185 mammographic examinations from January 1, 1985, to February 19, 2002. Data were collected from a database that had been assembled prospectively. Two categories of false-positive events were examined: biopsies that did not reveal cancer and false-positive mammographic assessments. Rates of false-positive events were compared by using a chi2 analysis, and 95% confidence limits were calculated. Because comparisons of multiple pairs were considered, all P values that demonstrated statistical significance exceeded the requirement of the Bonferroni correction. RESULTS: While the overall rates of biopsies that did not reveal cancer and of false-positive mammographic assessments were similar to those found in other studies, most of the burden of false-positive events was borne by women who underwent intermittent screening. Long-term rates of false-positive events were lower among women who underwent regular screening than among those who underwent intermittent screening. In the 5-year group, 2.9% of women who underwent five mammographic examinations over the next 5 years had biopsy results that did not reveal cancer, whereas 4.6% of women who underwent three mammographic examinations over the next 5 years had biopsy results that did not reveal cancer. For women who underwent regular screening, the risk of undergoing biopsies that did not reveal cancer declined over time to 0.25% per year after several years of screening, a value that is lower than the risk of these events among women who did not undergo screening. The rate of false-positive mammographic assessments was also lower for women who underwent regular screening than for those who underwent intermittent screening. CONCLUSION: Prompt annual attendance for mammographic screening reduces the occurrence of false-positive mammographic results.

Adult↗

PubMed2006

Evaluation of digital skin images submitted by patients who received practical training or an online tutorial.

We evaluated the ability of subjects to capture and submit teledermatology images with a digital camera. We also examined whether participants who received individual training sessions would capture better-quality images than participants who were provided only with self-training. Fifty participants were randomized between in-person training and self-training via an online tutorial. The majority of participants were young, well educated women. Two dermatologists reading the images for quality indicators had high agreement that digital images acquired were of high quality: images were well framed, appropriately bright, in focus and did not have a shadow. There was moderate agreement on diagnosis-related indicators, such as the presence or absence of pustules or papules and acne versus rosacea. There was no difference in the image-quality attributes between participants personally trained and those trained with the online tutorial. Subjects participating in this study were able to acquire images of good quality, irrespective of whether they received practical training or used an online tutorial.

Acne Vulgaris↗

PubMed2006

CT of colon cancer metastases to the liver using modified RECIST criteria: determining the ideal number of target lesions to measure.

OBJECTIVE: We sought to define the ideal number of target lesions to be measured to assess disease response in patients undergoing chemotherapy for colon cancer metastases to the liver. MATERIALS AND METHODS: Thirty consecutive patients were recruited for this study. Patients were part of a multisite, randomized, double-arm, phase 3 clinical trial involving chemotherapy with an investigational drug for metastatic colon cancer. Patients were recruited from U.S. and international sites. Institutional review board approval was obtained, and informed consent was obtained from all patients. Our study included CT measurements of hepatic metastases. All patients (n = 30) had a minimum of five target lesions in the liver. Target-lesion size was defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. We calculated the patient response at 2 months and at 6 months (complete response, partial response, stable disease, and progressive disease) using RECIST. Patient response was calculated based on the percentage increase or decrease at 2 and 6 months in the greatest diameter of the single largest lesion, two large lesions, three large lesions, four lesions, and five lesions, respectively. The concordance between five-target-lesion measurement and lesser numbers of lesions was analyzed using kappa statistics (StatView, 5.0). RESULTS: In 93.33% of patients (n = 28/30), there was agreement on patient response irrespective of the number of measurements made on CT. Of these 30 patients, 47% had a partial response (n = 14/30), 43% had stable disease (n = 13/30), and 10% had progressive disease at 2 months (n = 3/30). At 6 months, 43% had a partial response (n = 13/30), 47% had stable disease (n = 14/30), and 10% had progressive disease (n = 3/30). Agreement in response evaluation between lesion groups for multiple measurements was high, with values of 1.0 for multiple-lesion measurements and 0.88 for single-lesion measurements at 2 months. The concordance values were the same at 6 months. CONCLUSION: In the majority of patients with hepatic metastases of colorectal cancer, measuring the maximal diameter of the single largest lesion yielded the same treatment-response classification as measuring up to five target lesions. This result suggests that it may be possible to reduce the number of lesions measured in clinical trials.

Colonic Neoplasms↗

PubMed2006

Significance of incidental thyroid lesions detected on CT: correlation among CT, sonography, and pathology.

OBJECTIVE: The purpose of our study was to determine the prevalence of malignancy in incidental abnormalities of the thyroid gland detected on CT and to determine the relative accuracy of characterizing these abnormalities on CT as compared with sonography and pathology. MATERIALS AND METHODS: We searched our department's computerized clinical database for all thoracic and cervical CT scans in which a new abnormality was incidentally identified in the thyroid gland from 1998-2001. Two hundred thirty patients with abnormal findings in the gland on CT subsequently underwent thyroid sonography, and 118 of the 230 patients underwent a diagnostic biopsy or resection. CT and sonographic images were directly reviewed to identify imaging features of each thyroid abnormality, including the location, size, appearance, and presence or absence of calcifications. Associations were evaluated using Fisher's exact test of significance and the Student's t test. The overall rate of malignant and potentially malignant lesions among these incidental abnormalities of the thyroid gland was calculated. RESULTS: CT findings matched the sonographic characterization in 122 patients (53.0%), correctly identified the dominant nodule but missed multinodularity in 69 (30.0%) patients, and underestimated the number of nodules in 24 (10.4%) patients. CT overestimated the number of nodules in 5 (2.2%) patients and was false-positive for lesions in 10 patients (4.3%). Ninety-one patients with a single or dominant nodule on CT had pathologic correlation: 7 nodules were malignant, 17 showed malignant potential, and 67 were benign. Of 27 patients with multinodular or enlarged thyroid glands on CT and histopathologic correlation, 2 lesions were malignant and 25 benign. The presence of punctate calcifications on CT significantly correlated to the presence of microcalcifications on sonography (p < 0.02). Benign nodules were significantly smaller (mean, 2.16 +/- 1.01 cm; range, 0.6-4.5 cm) than malignant and potentially malignant nodules (mean, 2.79 +/- 0.99 cm; range, 0.7-4.6 cm) (p = 0.01). Patients 35 years or younger who had a thyroid lesion on CT were more likely to have malignancy (p < 0.01). Overall, among incidentally detected lesions of the thyroid gland, there was at least a 3.9% rate of malignancy (95% CI: 1.8-7.3%) and 7.4% rate of malignant potential (95% CI: 4.4-11.6%). CONCLUSION: There is at least an 11.3% prevalence of malignant or potentially malignant lesions among incidental thyroid abnormalities detected on CT. Patients 35 years or younger who have incidental abnormalities have a significantly greater rate of malignancy. No CT feature reliably distinguishes benign from malignant lesions in the thyroid gland. CT underestimates the number of nodules relative to sonography, which suggests that sonography is a useful adjunctive test after the incidental detection of a thyroid abnormality on CT.

Adult↗

PubMed2006

Optimal CT breathing protocol for combined thoracic PET/CT.

OBJECTIVE: The objective of this study was to determine the optimal breathing protocol for combined PET/CT scans of the thorax. SUBJECTS AND METHODS: Eighty combined PET/CT scans were obtained in 64 patients (30 women, 34 men; mean age, 57 years; range, 19-86 years). The 80 PET/CT scans consisted of five group of patients (16 PET/CT scans per group) who underwent whole-body combined 18F-FDG PET/CT with different CT breathing protocols: expiration, mid suspended breath-hold, quiet breathing, small breath in, and regular breath in. The quality of alignment was analyzed at the diaphragm, aortic arch, heart, thoracic spine, and lung apices using a scale of ratings from 1 (very poor) to 5 (excellent). The Kruskal-Wallis test was used to compare alignment between breathing protocols for each anatomic reference point. RESULTS: Alignment of the PET and CT data sets was excellent with three breathing protocols: expiration, mid suspended breath-hold, and quiet breathing, with no statistical differences. Significant misalignment occurred at the diaphragm (p < 0.0001) and heart (p < 0.0001) with the small breath-in and regular breath-in techniques. CONCLUSION: Excellent image fusion of combined PET/CT data sets in the thorax, especially at the diaphragm and heart, can be achieved with expiration, mid suspended breath-hold, or quiet breathing. Quiet breathing is recommended for optimal patient comfort during acquisition of attenuation-correction CT data sets.

Adult↗

PubMed2006

Optical coherence tomography to identify intramucosal carcinoma and high-grade dysplasia in Barrett's esophagus.

BACKGROUND & AIMS: Optical coherence tomography (OCT) is an optical technique that produces high-resolution images of the esophagus during endoscopy. OCT can distinguish specialized intestinal metaplasia (SIM) from squamous mucosa, but image criteria for differentiating intramucosal carcinoma (IMC) and high-grade dysplasia (HGD) from low-grade dysplasia (LGD), indeterminate-grade dysplasia (IGD), and SIM without dysplasia have not been validated. The purpose of this study was to establish OCT image characteristics of IMC and HGD in Barrett's esophagus. METHODS: Biopsy-correlated OCT images were acquired from patients with Barrett's esophagus undergoing endoscopic surveillance. Two pathologists rendered consensus diagnoses of the biopsy specimens. A blinded investigator reviewed the biopsy-correlated OCT images and scored each for surface maturation and gland architecture. For each image the scores were summed to determine an OCT "dysplasia index." RESULTS: A total of 177 biopsy-correlated images were analyzed. The corresponding histopathology diagnosis was IMC/HGD in 49 cases, LGD in 15, IGD in 8, SIM in 100, and gastric mucosa in 5. A significant relationship was found between a histopathologic diagnosis of IMC/HGD and scores for each image feature (dysplasia index [Spearman correlation coefficient, r = 0.50, P < .0001], surface maturation [r = 0.48, P < .0001], and gland architecture [r = 0.41, P < .0001]). When a dysplasia index threshold of >or=2 was used, the sensitivity and specificity for diagnosing IMC/HGD were 83% and 75%, respectively. CONCLUSIONS: An OCT image scoring system based on histopathologic characteristics has the potential to identify IMC and HGD in Barrett's esophagus.

Adult↗

PubMed2005

Distinguishing benign from malignant adrenal masses: multi-detector row CT protocol with 10-minute delay.

PURPOSE: To retrospectively evaluate the accuracy of precontrast attenuation, relative percentage washout (RPW), and absolute percentage washout (APW) in distinguishing benign from malignant adrenal masses at multi-detector row computed tomography (CT). MATERIALS AND METHODS: This HIPAA-compliant retrospective study had institutional review board approval; the need for informed consent was waived. One hundred twenty-two adrenal masses were evaluated in 99 patients (51 men, 48 women; age range, 37-86 years) who had undergone CT performed according to the study protocol and who either were given a pathologic diagnosis or underwent follow-up imaging. Unenhanced images were obtained before administration of 120 mL of an intravenous contrast agent with a 75-second scan delay. Delayed images were obtained after 10 minutes. RPW and APW were computed. Receiver operating characteristic (ROC) analysis was performed to compare mean attenuation and both RPW and APW. Analysis was first performed with the exclusion of pheochromocytomas, myelolipomas, and cysts. Precontrast attenuation criteria specific for benignity or malignancy were determined, and ROC analysis of results for the entire nonpheochromocytoma group was then performed. RESULTS: By using an RPW of 37.5% and excluding cysts and myelolipomas, all malignant lesions were detected with a sensitivity of 100% (17 of 17 lesions) and a specificity of 95% (90 of 95 lesions). Area under the binomial ROC curve (A(z)) values were 0.912, 0.985, and 0.892 for precontrast attenuation, RPW, and APW, respectively. Precontrast attenuation of less than 0 or more than 43 HU indicated benign and malignant entities, respectively. Incorporation of these criteria into the APW analysis yielded a sensitivity of 100% (17 of 17 lesions) and a specificity of 98% (93 of 95 lesions) for a threshold washout value of 52.0%. This attenuation-corrected APW generated the greatest A(z) value (ie, 0.988). Combining all the information available from the protocol yielded a sensitivity of 100% (17 of 17 lesions) and a specificity of 98% (98 of 100 lesions) for differentiating benign from malignant masses. CONCLUSION: Precontrast attenuation of less than 0 HU supercedes the washout profile in the evaluation of an individual adrenal mass. Noncalcified, nonhemorrhagic adrenal lesions with precontrast attenuation of more than 43 HU should be considered suspicious for malignancy.

Adrenal Gland Diseases↗

PubMed2005

Quantitative assessment of regional myocardial function in mice by tissue Doppler imaging: comparison with hemodynamics and sonomicrometry.

BACKGROUND: Tissue Doppler imaging (TDI) is a novel echocardiographic method to quantify regional myocardial function. The objective of this study was to assess whether myocardial velocities and strain rate (SR) could be obtained by TDI in mice and whether these indices accurately quantified alterations in left ventricular (LV) systolic function. METHODS AND RESULTS: TDI was performed in 10 healthy mice to measure endocardial (v(endo)) and epicardial systolic velocities and SR. In further experiments, TDI indices were compared with dP/dt(max) and with sonomicrometer-derived regional velocities, at rest and after administration of dobutamine or esmolol. TDI indices were also studied serially in 8 mice before and 4 and 7 hours after endotoxin challenge. Myocardial velocities and SR were obtained in all mice with low measurement variability. TDI indices increased with administration of dobutamine (v(endo) from 2.2+/-0.3 to 3.8+/-0.2 cm/s [P<0.01]; SR from 12+/-2 to 20+/-2 s(-1) [P<0.05]) and decreased with administration of esmolol (v(endo) 1.4+/-0.2 cm/s [P<0.05]; SR 6+/-1 s(-1) [P<0.01]). Both indices correlated strongly with dP/dt(max) (r2=0.79 for SR and r2= 0.69 for v(endo); both P<0.0001). SR and shortening fraction were predictors of dP/dt(max) even after adjustment for the confounding effect of the other variables. V(endo) correlated closely with sonomicrometer-measured velocity (r2=0.71, P<0.0005). After endotoxin challenge, decreases in both v(endo) and SR were detected before decreases in shortening fraction became manifest. CONCLUSIONS: Myocardial velocities and SR can be measured noninvasively in mice with the use of TDI. Both indices are sensitive markers for quantifying LV global and regional function in mice.

Animals↗