Piotr Obara

Epidermal growth factor receptor signaling is up-regulated in human colonic aberrant crypt foci.

Aberrant crypt foci (ACF) are collections of abnormal colonic crypts with heterogeneous molecular and pathologic characteristics. Large and dysplastic ACF are putative precursors of colon cancer with neoplastic risk related to increased proliferation. In this study, we examined the role of epidermal growth factor receptor (EGFR) signaling in regulating ACF proliferation. Using magnification chromoendoscopy, we collected large ACF with endoscopic features of dysplasia and separately biopsied adjacent mucosa. Transcript levels were measured by real-time PCR, proteins were assessed by Western blotting, and levels were expressed as fold changes of adjacent mucosa. K-ras and B-Raf mutations were assessed by PCR and Ras activation by the ratio Ras-GTP / (Ras-GTP + Ras-GDP). At the RNA level, 38% of ACF were hyperproliferative, with proliferating cell nuclear antigen (PCNA) mRNA >/=2-fold of adjacent mucosa. Hyperproliferative ACF had significantly increased mRNA levels of EGFR (6.0 +/- 1.7-fold), transforming growth factor-alpha (14.4 +/- 5.0-fold), heparin-binding EGF-like growth factor (4.5 +/- 1.4-fold), cyclin D1 (4.6 +/- 0.7-fold), and cyclooxygenase-2 (COX-2; 9.3 +/- 4.2-fold; P < 0.05). At the protein level, 46% of ACF were hyperproliferative (PCNA, 3.2 +/- 1.2-fold). In hyperproliferative ACF, 44% possessed significant increases in four EGFR signaling components: EGFR (9.5 +/- 1.3-fold), phosphoactive ErbB2 (2.6 +/- 0.4-fold), phosphoactive extracellular signal-regulated kinase (3.7 +/- 1.1-fold), and cyclin D1 (3.4 +/- 0.8-fold; P < 0.05). Ras was activated in 46% of ACF (3.2 +/- 0.4-fold; P < 0.05), but K-ras mutations were present in only 7% of ACF. In contrast to COX-2 mRNA, the protein was not increased in hyperproliferative ACF. In summary, we have shown that ACF with up-regulated PCNA possess increased EGFR signaling components that likely contribute to the enhanced proliferative state of dysplastic-appearing ACF.

Prospective Comparison of 99mTc-MDP Scintigraphy, Combined 18F-NaF and 18F-FDG PET/CT, and Whole-Body MRI in Patients with Breast and Prostate Cancer

We prospectively evaluated the use of combined 18F-NaF/18F-FDG PET/CT in patients with breast and prostate cancer and compared the results with those for 99mTc-MDP bone scintigraphy and whole-body MRI. Methods: Thirty patients (15 women with breast cancer and 15 men with prostate cancer) referred for standard-of-care bone scintigraphy were prospectively enrolled in this study. 18F-NaF/18F-FDG PET/CT and whole-body MRI were performed after bone scintigraphy. The whole-body MRI protocol consisted of both unenhanced and contrast-enhanced sequences. Lesions detected with each test were tabulated, and the results were compared. Results: For extraskeletal lesions, 18F-NaF/18F-FDG PET/CT and whole-body MRI had no statistically significant differences in sensitivity (92.9% vs. 92.9%, P = 1.00), positive predictive value (81.3% vs. 86.7%, P = 0.68), or accuracy (76.5% vs. 82.4%, P = 0.56). However, 18F-NaF/18F-FDG PET/CT showed significantly higher sensitivity and accuracy than whole-body MRI (96.2% vs. 81.4%, P < 0.001, 89.8% vs. 74.7%, P = 0.01) and bone scintigraphy (96.2% vs. 64.6%, P < 0.001, 89.8% vs. 65.9%, P < 0.001) for the detection of skeletal lesions. Overall, 18F-NaF/18F-FDG PET/CT showed higher sensitivity and accuracy than whole-body MRI (95.7% vs. 83.3%, P < 0.002, 87.6% vs. 76.0%, P < 0.02) but not statistically significantly so when compared with a combination of whole-body MRI and bone scintigraphy (95.7% vs. 91.6%, P = 0.17, 87.6% vs. 83.0%, P = 0.53). 18F-NaF/18F-FDG PET/CT showed no significant difference from a combination of 18F-NaF/18F-FDG PET/CT and whole-body MRI. No statistically significant differences in positive predictive value were noted among the 3 examinations. Conclusion: 18F-NaF/18F-FDG PET/CT is superior to whole-body MRI and 99mTc-MDP scintigraphy for evaluation of skeletal disease extent. Further, 18F-NaF/18F-FDG PET/CT and whole-body MRI detected extraskeletal disease that may change the management of these patients. 18F-NaF/18F-FDG PET/CT provides diagnostic ability similar to that of a combination of whole-body MRI and bone scintigraphy in patients with breast and prostate cancer. Larger cohorts are needed to confirm these preliminary findings, ideally using the newly introduced simultaneous PET/MRI scanners.

Evolving role of MRI in Crohn's disease

MR enterography is playing an evolving role in the evaluation of small bowel Crohns disease (CD). Standard MR enterography includes a combination of rapidly acquired T2 sequence, balanced steady‐state acquisition, and contrast enhanced T1‐weighted gradient echo sequence. The diagnostic performance of these sequences has been shown to be comparable, and in some respects superior, to other small bowel imaging modalities. The findings of CD on MR enterography have been well described in the literature. New and emerging techniques such as diffusion‐weighted imaging (DWI), dynamic contrast enhanced MRI (DCE‐MRI), cinematography, and magnetization transfer, may lead to improved accuracy in characterizing the disease. These advanced techniques can provide quantitative parameters that may prove to be useful in assessing disease activity, severity, and response to treatment. In the future, MR enterography may play an increasing role in management decisions for patients with small bowel CD; however, larger studies are needed to validate these emerging MRI parameters as imaging biomarkers. J. Magn. Reson. Imaging 2013;37:1277–1289.

Prognostic value of metabolic tumor burden in lung cancer

Accurate prognosis in patients with lung cancer is important for clinical decision making and treatment selection. The TNM staging system is currently the main method for establishing prognosis. Using this system, patients are grouped into one of four stages based on primary tumor extent, nodal disease, and distant metastases. However, each stage represents a range of disease extent and may not on its own be the best reflection of individual patient prognosis. (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) can be used to evaluate the metabolic tumor burden affecting the whole body with measures such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG). MTV and TLG have been shown to be significant prognostic factors in patients with lung cancer, independent of TNM stage. These metabolic tumor burden measures have the potential to make lung cancer staging and prognostication more accurate and quantitative, with the goal of optimizing treatment choices and outcome predictions.

Adenoma Localization for Recurrent or Persistent Primary Hyperparathyroidism Using Dynamic Four-Dimensional CT and Venous Sampling

PURPOSE To determine if parathyroid venous sampling (PVS) combined with four-dimensional (4D) computed tomography (CT) improves sensitivity and accuracy of identification of parathyroid adenoma in patients with recurrent or persistent primary hyperparathyroidism (pHPT) and negative technetium-99m methoxyisobutyl isonitrile ((99m)Tc-MIBI) and ultrasound (US) scans. MATERIALS AND METHODS Both PVS and 4D CT were performed in 28 patients with recurrent or persistent pHPT and negative (99m)Tc-MIBI and US examinations. Localization by 4D CT alone and in combination with PVS and lateralization by PVS alone were retrospectively assessed for correlation with surgical results. Suspected adenomas on 4D CT were said to correlate with PVS if venous drainage identified on CT corresponded to sites of elevated parathyroid hormone concentration on PVS. Lesions difficult to identify on 4D CT were lesions < 1 cm in longest dimension. Results of 4D CT were classified as positive, negative, or equivocal. RESULTS Surgery was performed in 22 of 28 patients. Surgery identified 23 parathyroid adenomas, 1 carcinoma, and 2 hyperplastic glands in 20 patients. 4D-CT alone localized 11 lesions in 10 patients. PVS helped localize 13 additional lesions in nine more patients and clarified two lesions that were equivocal on 4D CT. Comparing 4D CT alone with 4D CT plus PVS, the sensitivity increased from 50% to 95% (P = .004), and accuracy increased from 55% to 91% (P = .022). PVS lateralization had a sensitivity of 93.3%, positive predictive value of 66.7%, and accuracy of 63.6%. CONCLUSIONS PVS significantly improves 4D CT localization of parathyroid adenomas in patients undergoing repeat surgery for pHPT with negative (99m)Tc-MIBI and US.

BMI-based radiation dose reduction in CT colonography.

RATIONALE AND OBJECTIVES There is potential for x-ray dose reduction in computed tomography colonography (CTC) relative to body mass index (BMI). We evaluated the association between BMI and three-dimensional (3D) CTC image quality to assess the potential utility of BMI as the basis for radiation dose reduction in CTC. MATERIALS AND METHODS Ninety-six consecutive patients underwent CTC and were randomized for scanning at 15 or 30 mAs. Extremely obese patients (BMI > 50) were excluded. Each patient was scanned supine and prone on a multidetector CT scanner. Postprocessing CTC visualization was performed on a dedicated workstation. Three independent observers assessed 3D image quality using a four-point scale. Image noise was measured in both the abdomen and pelvis. The association between BMI and image noise was examined using random-effects linear regression models. Logistic regression was used to examine the relationship between BMI, mAs, and conspicuity scores. RESULTS Statistically significant differences in image noise were observed between 15 and 30 mAs in both the abdomen and pelvis, and the difference was greater with increasing BMI. A positive relationship was detected between BMI and noise in the abdomen (P < .001) and pelvis (P < .001). Inverse correlation was identified between BMI and conspicuity scores in the abdomen (P = .01) and pelvis (P < .001). Overall conspicuity scores were reduced for both 15 and 30 mAs groups as BMI increased. CONCLUSION The radiation dose for CTC can be reduced by 40% and 70% below commonly employed doses for overweight and normal BMI patients, respectively, by using a BMI-adjusted dose reduction approach. Conspicuity scores dropped in obese patients with reduced dose suggesting that standard accepted doses should be utilized in that group.

Quantification of metabolic tumor activity and burden in patients with non-small-cell lung cancer: Is manual adjustment of semiautomatic gradient-based measurements necessary?

PURPOSE Metabolic tumor burden (MTB) measurements including metabolic tumor volume and total lesion glycolysis have been shown to have prognostic value in non-small-cell lung cancer (NSCLC). The calculation of MTB typically utilizes software to semiautomatically draw volumes of interest around the tumor, which are subsequently manually adjusted by the radiologist to include the entire tumor. The manual adjustment step can be time-consuming and observer-dependent. We compared the agreement of MTB values obtained using the semiautomatic method with and without manual adjustment in NSCLC patients. METHODS This IRB-approved prospective study included 134 patients with histologically proven NSCLC who underwent fluorine-18 fluorodeoxyglucose PET/computed tomography. The MTB of the primary tumor was measured with a semiautomatic gradient-based method without manual adjustment (the semiautomatic gradient method) and with manual adjustment (the manually adjusted semiautomatic gradient method) by two radiologists using the MIM PETedge tool. The paired t-test, Wilcoxon signed-rank test, and concordance correlation coefficient (CCC) were calculated to evaluate the agreement between MTB measures obtained with these two methods, as well as agreement between the two radiologists for each method. RESULTS Maximum standardized uptake value was identical between the two methods. No statistically significant difference was present for peak standardized uptake value, metabolic tumor volume, and total lesion glycolysis values between the two methods (P=0.23, 0.45, and 0.37, respectively). Excellent agreement between the two methods was found in terms of CCC (CCC>0.98 for all measures). Interobserver reliability was excellent for all measures (CCC>0.90). CONCLUSION The semiautomatic gradient-based tumor-segmentation method can be used without the additional manual adjustment step for MTB quantification of primary NSCLC tumors.

Evaluation of CT as a predictor for kidney and renal artery mobility.

PURPOSE Renal artery stent failure may result from excessive kidney mobility in some patients. We used computed tomography (CT) to determine the prevalence and magnitude of renal displacement due to postural changes. MATERIALS AND METHODS A retrospective review of 100 consecutive CT colonography examinations was performed to measure renal artery location and displacement in both axial and coronal views using paired supine and prone non-contrast scans. Kidney displacement from the prone to supine position was correlated with a change in renal artery angular deviation. Statistical significance was determined using t-tests and Pearson correlations. Results were based on measurements made by a single observer. RESULTS Mobility and angular displacement between the prone and supine positions were significant bilaterally and in both planes (P < 0.01) except for the coronal plane kidney mobility on the left (P = 0.32). The axial plane correlation between kidney and artery mobility was significant bilaterally (left/right R=0.44/0.22, P < 0.01/0.03); the coronal plane correlation was only significant on the left (left/right R=0.26/0.18, P = 0.01/0.08). The mean axial plane mobility and angle change were greater on the left (left/right mobility 13 mm/7 mm; left/right angle change 18°/8°). In contrast, the mean coronal plane mobility and angle change were greater on the right (left/right mobility 4 mm/22 mm; left/right angle change 4°/8°). Fourteen patients had a mobility in excess of 32°. CONCLUSION During postural changes, the kidneys and renal arteries demonstrate significant correlated mobility. Renal artery movements can be identified using a low-radiation dose CT exam.

The impact of computed high b-value images on the diagnostic accuracy of DWI for prostate cancer: A receiver operating characteristics analysis

To evaluate the performance of computed high b value diffusion-weighted images (DWI) in prostate cancer detection. 97 consecutive patients who had undergone multiparametric MRI of the prostate followed by biopsy were reviewed. Five radiologists independently scored 138 lesions on native high b-value images (b = 1200 s/mm2), apparent diffusion coefficient (ADC) maps, and computed high b-value images (contrast equivalent to b = 2000 s/mm2) to compare their diagnostic accuracy. Receiver operating characteristic (ROC) analysis and McNemar’s test were performed to assess the relative performance of computed high b value DWI, native high b-value DWI and ADC maps. No significant difference existed in the area under the curve (AUC) for ROCs comparing B1200 (b = 1200 s/mm2) to computed B2000 (c-B2000) in 5 readers. In 4 of 5 readers c-B2000 had significantly increased sensitivity and/or decreased specificity compared to B1200 (McNemar’s p < 0.05), at selected thresholds of interpretation. ADC maps were less accurate than B1200 or c-B2000 for 2 of 5 readers (P < 0.05). This study detected no consistent improvement in overall diagnostic accuracy using c-B2000, compared with B1200 images. Readers detected more cancer with c-B2000 images (increased sensitivity) but also more false positive findings (decreased specificity).

ACR Appropriateness Criteria® Lower Extremity Arterial Revascularization—Post-Therapy Imaging

Peripheral arterial disease (PAD) affects millions across the world and in the United States between 9% to 23% of all patients older than 55 years. The refinement of surgical techniques and evolution of endovascular approaches have improved the success rates of revascularization in patients afflicted by lower extremity PAD. However, restenosis or occlusion of previously treated vessels remains a pervasive issue in the postoperative setting. A variety of different imaging options are available to evaluate patients and are reviewed within the context of asymptomatic and symptomatic patients with PAD who have previously undergone endovascular or surgical revascularization. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.