Hybrid magnetic resonance and PET imaging for prostate cancer recurrence.

PURPOSE OF REVIEW: Recurrence post definitive local therapy by prostatectomy or radiation therapy is often detected via rise in serum prostate-specific antigen (PSA) levels; however, PSA rise does not localize the disease. Distinguishing local versus distant recurrence guides whether to choose subsequent local versus systemic therapy. The purpose of this article is to review imaging for prostate cancer recurrence post local therapy. RECENT FINDINGS: Among imaging modalities, multiparametric MRI (mpMRI) is commonly used to assess for local recurrence. New radiopharmaceuticals target prostate cancer cells and enable whole-body imaging. These tend to be more sensitive for lymph node metastases than MRI or computed tomography (CT) and for bone lesions than bone scan at lower PSA levels but can be limited for local prostate cancer recurrence. Given greater soft tissue contrast, similar criteria for lymph nodes, and greater sensitivity for prostate bone metastases, MRI is advantageous to CT. MRI of the whole body and mpMRI are now feasible within a reasonable time frame and complementary to PET imaging, enabling whole-body and pelvis-focused PET-MRI, which should be advantageous in the setting of recurrent prostate cancer. SUMMARY: Hybrid PET-MRI with prostate cancer targeted radiopharmaceuticals and whole body with local multiparametric MRI can be complementary for detecting local and distant recurrence to guide treatment planning.

Indocyanine Green (ICG) Fluorescence Is Dependent on Monomer with Planar and Twisted Structures and Inhibited by H-Aggregation.

The optical properties of indocyanine green (ICG) as a near-infrared (NIR) fluorescence dye depend on the nature of the solvent medium and the dye concentration. In the ICG absorption spectra of water, at high concentrations, there were absorption maxima at 700 nm, implying H-aggregates. With ICG dilution, the main absorption peak was at 780 nm, implying monomers. However, in ethanol, the absorption maximum was 780 nm, and the shapes of the absorption spectra were identical regardless of the ICG concentration, indicating that ICG in ethanol exists only as a monomer without H-aggregates. We found that emission was due to the monomer form and decreased with H-aggregate formation. In the fluorescence spectra, the 820 nm emission band was dominant at low concentrations, whereas at high concentrations, we found that the emission peaks were converted to 880 nm, suggesting a new form via the twisted intramolecular charge transfer (TICT) process of ICG. The NIR fluorescence intensity of ICG in ethanol was approximately 12- and 9-times brighter than in water in the NIR-I and -II regions, respectively. We propose an energy diagram of ICG to describe absorptive and emissive transitions through the ICG structures such as the monomer, H-aggregated, and TICT monomer forms.

Prostate cancer grade downgrading at time of prostatectomy provides risk-stratification insight into future tumor behavior after prostatectomy.

BACKGROUND: Prostate biopsy (Bx) sampling-based diagnosis of prostate cancer (PCa) has well-described inaccuracy when compared against whole gland analysis upon prostatectomy. Although upgrading of PCa Grade Group (GG) is often described, the occurrence and prognostic implications of downgrading PCa GG at the time of radical prostatectomy (RP) is less understood. Our objective was to evaluate whether downgrading PCa GG at the time of RP was associated with future tumor behavior. METHODS: The SEER database was searched from 2010 to 2017 and patients were included if they were assigned pathological grades on both Bx and RP specimen. Patients were stratified into Bx GG > RP GG and Bx GG ≤ RP GG groups, and tumor behavior after treatment was examined. Cox regression was used for the survival analysis. RESULTS: Here, 99,835 patients were included in this study. A total of 18,516 (18.5%) patients encountered downgrading from Bx GG to RP GG. A downgrading of 1 grade occurred in 13,969 (75.4%) of these patients and of 2 or more grades occurred in 4547 (24.6%) patients. A history of higher Bx GG compared with RP GG increased the risk of cancer-specific mortality (CSM) for each given RP GG controlling for age, race, preop prostate-specific antigen level, percentage of positive biopsy cores, and pathologic TNM stages. Specifically, a history of high Bx GG conferred a 45% increased risk of CSM for any given RP GG (hazard ratio = 1.45 95% confidence interval = 1.16-1.82, p < 0.001). CONCLUSION: A history of higher Bx GG, and hence downgrading at the time of RP, demonstrates some value as a risk-stratification tool for future cancer outcomes after prostatectomy.

Performance of Multidetector Computed Tomography and Negative Versus Positive Enteric Contrast for Evaluation of Gastrointestinal Neuroendocrine Neoplasms.

BACKGROUND: Routine computed tomography (CT) scans are thought to have poor performance for detection of gastrointestinal (GI) neuroendocrine neoplasms (NENs), which leads to delayed workup. Detection of even 1 bowel tumor can guide diagnostic workup and management. The purposes of this study were to assess the accuracy of multidetector computed tomography (MDCT) and to compare negative versus positive enteric contrast in detecting at least 1 GI tumor per patient with suspected or confirmed diagnosis of a NEN. METHODS: This retrospective study included 107 patients with intravenous and oral contrast (65 positive, 40 negative, and 2 no oral contrast) abdominopelvic MDCT. Two abdominal radiologists independently analyzed the CTs for detection and localization of bowel NENs. Surgical pathology was considered the reference standard. Analyses included κ and summary statistics, McNemar test, Pearson χ2 test, and Fisher exact test. RESULTS: Among the 107 CT scans, there were 30 pathology negative studies and 77 studies with positive pathology for GI NEN. Interreader agreement for CT evaluation was substantial (κ = 0.61). At least 1 GI NEN per patient was detected with 51% to 53% sensitivity, 87% to 93% specificity, 91% to 95% positive predictive value (PPV), 42% negative predictive value, and 63% accuracy for each reader, and 57% accuracy when only the concordant (ie, matching) results of the 2 readers were considered. Computed tomography scans with negative enteric contrast had significantly higher sensitivity for concordant results than CTs with positive enteric contrast (58% vs 30%, P = 0.01). Specificity (100% vs 95%, P = 0.5), PPV (100% vs 93%, P = 0.49), negative predictive value (39% vs 39%, P = 0.99), and accuracy (67% vs 51%, P = 0.10) were not significantly different for negative versus positive enteric contrast for the concordant results. There was no significant difference in GI NEN localization between the readers. CONCLUSIONS: Routine MDCT with either positive or negative enteric contrast can detect at least 1 GI tumor per patient with more than 90% PPV and more than 50% accuracy in patients suspected of GI NEN. Using negative enteric contrast improves sensitivity for GI NEN versus positive enteric contrast. In addition, there is high accuracy in localizing the bowel tumor with positive or negative enteric contrast, which may guide surgery. Radiologists should have heightened awareness that evaluating such scans closely may lead to detection of primary bowel NENs at a higher rate than previously reported.

Bempegaldesleukin (BEMPEG; NKTR-214) efficacy as a single agent and in combination with checkpoint-inhibitor therapy in mouse models of osteosarcoma.

Survival of patients with relapsed/refractory osteosarcoma has not improved in the last 30 years. Several immunotherapeutic approaches have shown benefit in murine osteosarcoma models, including the anti-programmed death-1 (anti-PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) immune checkpoint inhibitors. Treatment with the T-cell growth factor interleukin-2 (IL-2) has shown some clinical benefit but has limitations due to poor tolerability. Therefore, we evaluated the efficacy of bempegaldesleukin (BEMPEG; NKTR-214), a first-in-class CD122-preferential IL-2 pathway agonist, alone and in combination with anti-PD-1 or anti-CTLA-4 immune checkpoint inhibitors in metastatic and orthotopic murine models of osteosarcoma. Treatment with BEMPEG delayed tumor growth and increased overall survival of mice with K7M2-WT osteosarcoma pulmonary metastases. BEMPEG also inhibited primary tumor growth and metastatic relapse in lungs and bone in the K7M3 orthotopic osteosarcoma mouse model. In addition, it enhanced therapeutic activity of anti-CTLA-4 and anti-PD-1 checkpoint blockade in the DLM8 subcutaneous murine osteosarcoma model. Finally, BEMPEG strongly increased accumulation of intratumoral effector T cells and natural killer cells, but not T-regulatory cells, resulting in improved effector:inhibitory cell ratios. Collectively, these data in multiple murine models of osteosarcoma provide a path toward clinical evaluation of BEMPEG-based regimens in human osteosarcoma.

Imaging Biochemical Recurrence After Prostatectomy: Where Are We Headed?

OBJECTIVE. In this article, we discuss the evolving roles of imaging modalities in patients presenting with biochemical recurrence after prostatectomy. CONCLUSION. Multiple imaging modalities are currently available to evaluate patients with prostate cancer presenting with biochemical recurrence after prostatectomy. Multiparametric MRI (mpMRI) focuses on the postsurgical bed as well as regional lymph nodes and bones. PET/CT studies using 18F-fluciclovine, 11C-choline, and prostate-specific membrane antigen (PSMA) ligands are useful in detecting locoregional and distant metastasis. Multiparametric MRI is preferred for patients with low risk of metastasis for localizing recurrence in prostate bed as well as pelvic lymph node and bone recurrence. Moreover, mpMRI aids in guiding biopsy and additional salvage treatments. For patients with high risk of metastatic disease, both mpMRI and whole-body PET/CT may be performed. PET/MRI using 68Ga-PSMA has potential to enable a one-stop shop for local recurrence and metastatic disease evaluation, and clinical trials of PET/MRI are ongoing.

Effects of excitation angle strategy on quantitative analysis of hyperpolarized pyruvate.

PURPOSE: Various excitation strategies have been proposed for dynamic imaging of hyperpolarized agents such as [1-13 C]-pyruvate, but the impact of these strategies on quantitative evaluation of signal evolution remains unclear. To better understand their relative performance, we compared the accuracy and repeatability of measurements made using variable excitation angle strategies and conventional constant excitation angle strategies. METHODS: Signal evolution for constant and variable excitation angle schedules was simulated using a pharmacokinetic model of hyperpolarized pyruvate with 2 chemical pools and 2 physical compartments. Noisy synthetic data were then fit using the same pharmacokinetic model with the apparent chemical exchange term as an unknown, and fit results were compared with simulation parameters to determine accuracy and reproducibility. RESULTS: Constant excitations and a variable excitation strategy that maximizes the HP lactate signal yielded data that supported quantitative analyses with similar accuracy and repeatability. Variable excitation angle strategies that were designed to produce a constant signal level resulted in lower signal and worse quantitative accuracy and repeatability, particularly for longer acquisition times. CONCLUSIONS: These results suggest that either constant excitation angle or variable excitation angles that attempt to maximize total signal, as opposed to maintaining a constant signal level, are preferred for metabolic quantification using hyperpolarized pyruvate.

Metformin Reduces Renal Uptake of Radiotracers and Protects Kidneys from Radiation-Induced Damage.

Metformin is the most widely prescribed drug for type 2 diabetes. Chemically, metformin is a hydrophilic base that functions as an organic cation, suggesting that it may have the capacity to inhibit the tubular reabsorption of peptide radiotracers. The purpose of this study was to investigate whether metformin could reduce renal uptake of peptidyl radiotracers and serve as a radioprotective agent for peptide receptor radionuclide therapy (PRRT). METHODS: We used two radiolabeled peptides: a 68Ga-labeled cyclic (TNYL-RAW) peptide (68Ga-NOTA-c(TNYL-RAW) (NOTA: 1,4,7 triazacyclononane-1,4,7-trisacetic acid) targeting EphB4 receptors and an 111In- or 64Cu-labeled octreotide (111In/64Cu-DOTA-octreotide) (DOTA: 1,4,7,10 triazacyclododecane-1,4,7,10-tetraacetic acid) targeting somatostatin receptors. Each radiotracer was injected intravenously into normal Swiss mice or tumor-bearing nude mice in the presence or absence of metformin administered intravenously or orally. Micropositron emission tomography or microsingle-photon emission computed tomography images were acquired at different times after radiotracer injection, and biodistribution studies were performed at the end of the imaging session. To assess the radioprotective effect of metformin on the kidneys, normal Swiss mice received two doses of 111In-DOTA-octreotidein the presence or absence of metformin, and renal function was analyzed via blood chemistry and histology. RESULTS: Intravenous injection of metformin with 68Ga-NOTA-c(TNYL-RAW) or 111In-DOTA-octreotide reduced the renal uptake of the radiotracer by 60% and 35%, respectively, compared to uptake without metformin. These reductions were accompanied by greater uptake in the tumors for both radiolabeled peptides. Moreover, the renal uptake of 111In-DOTA-octreotide was significantly reduced when metformin was administered via oral gavage. Significantly more radioactivity was recovered in the urine collected over a period of 24 h after intravenous injection of 64Cu-DOTA-octreotide in mice that received oral metformin than in mice that received vehicle. Finally, coadministration of 111In-DOTA-octreotide with metformin mitigated radio-nephrotoxicity. CONCLUSION: Metformin inhibits kidney uptake of peptidyl radiotracers, protecting the kidney from nephrotoxicity. Further studies are needed to elucidate the mechanisms of these finding and to optimize mitigation of radiation-induced damage to kidney in PRRT.

In Vivo Assessment of Ovarian Tumor Response to Tyrosine Kinase Inhibitor Pazopanib by Using Hyperpolarized 13C-Pyruvate MR Spectroscopy and 18F-FDG PET/CT Imaging in a Mouse Model.

Purpose To assess in a mouse model whether early or late components of glucose metabolism, exemplified by fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) and hyperpolarized carbon 13 (13C)-pyruvate magnetic resonance (MR) spectroscopy, can serve as indicators of response in ovarian cancer to multityrosine kinase inhibitor pazopanib. Materials and Methods In this Animal Care and Use Committee approved study, 17 days after the injection of 2 × 106 human ovarian SKOV3 tumors cells into 14 female nude mice, treatment with vehicle or pazopanib (2.5 mg per mouse peroral every other day) was initiated. Longitudinal T2-weighted MR imaging, dynamic MR spectroscopy of hyperpolarized pyruvate, and 18F-FDG PET/computed tomographic (CT) imaging were performed before treatment, 2 days after treatment, and 2 weeks after treatment. Results Pazopanib inhibited ovarian tumor growth compared with control (0.054 g ± 0.041 vs 0.223 g ± 0.112, respectively; six mice were treated with pazopanib and seven were control mice; P < .05). Significantly higher pyruvate-to-lactate conversion (lactate/pyruvate + lactate ratio) was found 2 days after treatment with pazopanib than before treatment (0.46 ± 0.07 vs 0.31 ± 0.14, respectively; P < .05; six tumors after treatment, seven tumors before treatment). This was not observed with the control group or with 18F-FDG PET/CT imaging. Conclusion The findings suggest that hyperpolarized 13C-pyruvate MR spectroscopy may serve as an early indicator of response to tyrosine kinase (angiogenesis) inhibitors such as pazopanib in ovarian cancer even when 18F-FDG PET/CT does not indicate a response. © RSNA, 2017 Online supplemental material is available for this article.

Can reduced field-of-view diffusion sequence help assess microsatellite instability in FIGO stage 1 endometrial cancer?

PURPOSE: To determine if a reduced-field-of-view (rFOV) diffusion intravoxel incoherent motion (IVIM) sequence can differentiate the imaging characteristics of tumors with microsatellite instability (MSI) from those that are microsatellite stable (MSS) in patients with clinical FIGO stage IA endometrial cancer and if MRI can be used to determine MSI status. MATERIALS AND METHODS: Sagittal rFOV diffusion-weighted images were obtained in 12 patients on a 3T scanner using six b-values (0, 50, 100, 150, 200, and 600). These images were used to derive apparent diffusion coefficient (ADC), true diffusion coefficient (Dt ), pseudodiffusion (D*), and perfusion fraction (f). Regions of interest (ROIs) were drawn on the dynamic contrast-enhanced magnetic resonance imaging (MRI) sequence on an Advantage Windows workstation and were copied to the same location on IVIM-derived images. The ROI mean of these images was recorded and compared with the microsatellite status. The depth of myometrial invasion and IVIM-derived parameters were tabulated by microsatellite status. The Wilcoxon rank sum test was used to compare T1 postcontrast images and IVIM-derived images and microsatellite status. RESULTS: Six patients had MSS tumors and six had MSI tumors. MSS tumors had a significantly higher ADC value (P = 0.03) and Dt (P = 0.045) than the MSI tumors. There was no association between < and ≥ 50% depth of myometrial invasion (measured on pathology and MRI analysis) and MSI stability P > 0.99. CONCLUSION: IVIM, ADC and Dt may be able to determine microsatellite status noninvasively in patients with clinical FIGO stage I endometrial cancer. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:1216-1224.

Renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion: imaging findings in 21 patients.

OBJECTIVES: To characterize imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE gene fusion. METHODS: Twenty-one patients with Xp11.2/TFE RCC were retrospectively evaluated. Tumour location, size, density, cystic or solid appearance, calcification, capsule sign, enhancement pattern and metastases were assessed. RESULTS: Fourteen women and seven men were identified with 12 being 25 years old or younger. Tumours were solitary and cystic-solid (76.2 %) masses with a capsule (76.2 %); 90.5 % were located in the medulla. Calcifications and lymph node metastases were each observed in 24 %. On unenhanced CT, tumour attenuation was greater than in normal renal parenchyma (85.7 %). Tumour enhancement was less than in normal renal cortex on all enhanced phases, greater than in normal renal medulla on cortical and medullary phases, but less than in normal renal medulla on delayed phase. On MR, the tumours were isointense on T1WI, heterogeneously hypointense on T2WI and slightly hyperintense on diffusion-weighted imaging. CONCLUSION: Xp11.2/TFE RCC usually occurs in young women. It is a cystic-solid, hyperdense mass with a capsule. It arises from the renal medulla with enhancement less than in the cortex but greater than in the medulla in all phases except the delayed phase, when it is lower than in the medulla. KEY POINTS: • Xp11.2/TFE RCC was more prevalent in young women. • On unenhanced CT, Xp11.2/TFE RCC attenuation was greater than in renal parenchyma. • Xp111/2TFE RCC arises primarily from the renal medulla. • Xp11.2/TFE RCC enhancement was less than in the cortex on all phases. • Enhancement was greater than in the medulla in arterial and corticomedullary phase.

Pattern and Distribution of Distant Metastases in Anaplastic Prostate Carcinoma: A Single-Institute Experience With 101 Patients.

OBJECTIVE: The aim of this study was to evaluate the sites and frequencies of distant metastases in patients with anaplastic prostate carcinoma and to correlate those findings with prostate-specific antigen (PSA) levels. MATERIALS AND METHODS: Patients with anaplastic prostate carcinoma (n = 101) underwent CT and bone scans before platinum-based chemotherapy. CT findings were retrospectively reviewed to identify the sites of metastases. CT findings were correlated with baseline PSA levels. The Wilcoxon rank sum test was used to correlate PSA levels between patients with metastases at osseous and nonosseous sites. The Wilcoxon rank sum test was also used to correlate the type of bone metastases (blastic vs lytic) and the PSA levels. RESULTS: Eighty-three of 101 patients (82%) had osseous metastases. PSA levels were significantly higher in patients with bone metastases than in patients without osseous metastases. However, 23 of the 83 patients (28%) with bone metastases had PSA levels in the normal range (i.e., < 4 ng/mL). The type of bone metastases (blastic vs lytic) did not show any statistically significant correlation to the PSA levels. Overall, 63 of 101 patients (62%) had nonosseous distant metastases at one or more sites, including the liver (n = 34), lung (n = 24), mediastinum (n = 31), pleura (n = 7), brain (n = 9), adrenal glands (n = 6), peritoneum (n = 4), and spleen (n = 1). PSA levels were not significantly elevated in patients with nonosseous distant metastases. Twenty-six of the 63 patients (41%) with nonosseous metastases had PSA levels in the normal range (< 4 ng/mL). CONCLUSION: Patients with the anaplastic clinical variant of prostate cancer have a high frequency of typical and atypical sites of metastases. Common sites of nonosseous distant metastases include the liver, lung, mediastinum, pleura, brain, and adrenal glands. PSA levels are unreliable and may be disproportionately low, despite the presence of multifocal large-volume metastases. CT of the chest, abdomen, and pelvis should be considered in routine staging and follow-up of patients with anaplastic prostate carcinoma regardless of their PSA levels.

Role of Imaging in the Local Staging of Urothelial Carcinoma of the Bladder.

OBJECTIVE: The purpose of this article is to review imaging modalities used in local staging of bladder urothelial carcinoma. CONCLUSION: Urothelial carcinoma is the most common histologic subtype of bladder cancer, and accurate local staging of this tumor is crucial for management. Traditionally, local staging relied on biopsy. With increasing accuracy of imaging modalities and techniques, imaging also plays an important role in the multidisciplinary care of patients with this disease.

The ABCs of BHD: An In-Depth Review of Birt-Hogg-Dubé Syndrome.

OBJECTIVE: Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant inherited syndrome involving multiple organs. In young patients, renal neoplasms that are multiple, bilateral, or both, such as oncocytomas, chromophobe renal cell carcinoma (RCC), hybrid chromophobe RCC-oncocytomas, clear cell RCC, and papillary RCC, can suggest BHD syndrome. Extrarenal findings, including dermal lesions, pulmonary cysts, and spontaneous pneumothoraces, also aid in diagnosis. CONCLUSION: Radiologists may be one of the first medical specialists to suggest the diagnosis of BHD syndrome. Knowledge of pathogenesis and management, including the importance of the types of renal neoplasms in a given patient, is needed to properly recognize this rare condition.

Feasibility of a reduced field-of-view diffusion-weighted (rFOV) sequence in assessment of myometrial invasion in patients with clinical FIGO stage I endometrial cancer.

PURPOSE: To compare the clinical usefulness of reduced field-of-view diffusion-weighted imaging (rFOV) with other imaging techniques in determining the depth of myometrial invasion (DMI) in endometrial cancer. MATERIALS AND METHODS: In this prospective study we reviewed 3T magnetic resonance images of 51 patients with clinical Stage I endometrial cancer who underwent total abdominal hysterectomy with bilateral salphingoopherectomy within 3 days after imaging. rFOV with apparent diffusion coefficient reconstruction was obtained in three standard planes followed by sagittal T2 -weighted (T2 WI) images and 3D dynamic T1 -weighted and contrast-enhanced imaging (DCE MRI). Two radiologists with expertise in imaging gynecologic cancers evaluated images independently. The DMI was recorded on imaging and correlated with surgical pathology results. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for DMI were calculated (<50% vs. >50%). RESULTS: Compared with sagittal T2 WI + DCE MRI, rFOV imaging yielded greater specificity (82.2% vs. 90.0%, positive predictive value (42.8% vs. 60.0%), and accuracy (84.0% vs. 92%) for DMI determined by reader 1 and greater the sensitivity (83.3% vs. 100%) for DMI determined by reader 2. The error of measurement of DMI as a continuous variable in millimeters did not differ significantly between the rFOV and pathology results (P < 0.21). However, there was a statistically significant difference for the DMI measured on the dynamic sequence. The DMI on DCE was greater than that seen on pathology at P = 0.02. CONCLUSION: rFOV can be used to assess DMI in clinical Stage I endometrial cancer.

Dose reduction in CT urography and vasculature phantom studies using model-based iterative reconstruction.

To evaluate the feasibility of radiation dose reduction using model-based iterative reconstruction (MBIR) for evaluating the ureters and vasculature in a phantom, a tissue-equivalent CT dose phantom was scanned using a 64-channel CT scan-ner. Tubes of varying diameters filled with different dilutions of a contrast agent, simulating ureters or vessels, were inserted into the center of the phantom. Each combination was scanned using an existing renal protocol at 140 kVp or 120 kVp, yielding a display volumetric CT dose index (CTDIvol) of 24 mGy. The scans were repeated using reduced scan techniques to achieve lower radiation doses down to 0.8 mGy. The images were reconstructed using filtered back-projection (FBP) and model-based iterative reconstruction (MBIR). The noise and contrast-to-noise ratio (CNR) was measured for each contrast object. Comparisons between the two reconstruction methods at different dose levels were evaluated using a factorial design. At each CTDIvol the measured image noise was lower using MBIR compared to FBP (p < 0.0001). At low doses, the percent change in measured image noise between FBP and MBIR was larger. For the 12 mm object simulating a ureter or large vessel with an HU of 600, the measured CNR using MBIR at a CTDIvol of 1.7 mGy was greater than the CNR of FBP at a CTIDvol of 24 mGy (p < 0.0001). For the 5 mm object simulating a medium-sized vessel with a HU of 250, the mea-sured CNR using MBIR at a CTDIvol of 1.7 mGy was equivalent to that of FBP at a CTDIvol of 24 mGy. For the 2 mm, 100 HU object simulating a small vessel, the measured CNR using MBIR at a CTDIvol of 1.7 mGy was equivalent to that of FBP at a CTDIvol of 24 mGy. Low-dose (3.6 mGy) CT imaging of vasculature and ureter phantoms using MBIR results in similar noise and CNR compared to FBP at approximately one-sixth the dose. This suggests that, using MBIR, a one milliSievert exam of the ureters and vasculature may be clinically possible whilst still maintaining adequate image quality.

Performance evaluation of iterative reconstruction algorithms for achieving CT radiation dose reduction - a phantom study.

The purpose of this study was to characterize image quality and dose performance with GE CT iterative reconstruction techniques, adaptive statistical iterative recontruction (ASiR), and model-based iterative reconstruction (MBIR), over a range of typical to low-dose intervals using the Catphan 600 and the anthropomorphic Kyoto Kagaku abdomen phantoms. The scope of the project was to quantitatively describe the advantages and limitations of these approaches. The Catphan 600 phantom, supplemented with a fat-equivalent oval ring, was scanned using a GE Discovery HD750 scanner at 120 kVp, 0.8 s rotation time, and pitch factors of 0.516, 0.984, and 1.375. The mA was selected for each pitch factor to achieve CTDIvol values of 24, 18, 12, 6, 3, 2, and 1 mGy. Images were reconstructed at 2.5 mm thickness with filtered back-projection (FBP); 20%, 40%, and 70% ASiR; and MBIR. The potential for dose reduction and low-contrast detectability were evaluated from noise and contrast-to-noise ratio (CNR) measurements in the CTP 404 module of the Catphan. Hounsfield units (HUs) of several materials were evaluated from the cylinder inserts in the CTP 404 module, and the modulation transfer function (MTF) was calculated from the air insert. The results were con-firmed in the anthropomorphic Kyoto Kagaku abdomen phantom at 6, 3, 2, and 1mGy. MBIR reduced noise levels five-fold and increased CNR by a factor of five compared to FBP below 6mGy CTDIvol, resulting in a substantial improvement in image quality. Compared to ASiR and FBP, HU in images reconstructed with MBIR were consistently lower, and this discrepancy was reversed by higher pitch factors in some materials. MBIR improved the conspicuity of the high-contrast spatial resolution bar pattern, and MTF quantification confirmed the superior spatial resolution performance of MBIR versus FBP and ASiR at higher dose levels. While ASiR and FBP were relatively insensitive to changes in dose and pitch, the spatial resolution for MBIR improved with increasing dose and pitch. Unlike FBP, MBIR and ASiR may have the potential for patient imaging at around 1 mGy CTDIvol. The improved low-contrast detectability observed with MBIR, especially at low-dose levels, indicate the potential for considerable dose reduction.

PBI-05204, a supercritical CO2 extract of Nerium oleander, inhibits growth of human pancreatic cancer via targeting the PI3K/mTOR pathway.

Introduction Oleandrin, a cardiac glycoside, exerts strong anti-proliferative activity against various human malignancies in in vitro cells. Here, we report the antitumor efficacy of PBI-05204, a supercritical C02 extract of Nerium oleander containing oleandrin, in a human pancreatic cancer Panc-1 orthotopic model. Results While all the control mice exhibited tumors by the end of treatment, only 2 of 8 mice (25%) treated for 6 weeks with PBI-05204 (40 mg/kg) showed dissectible tumor at the end of the treatment period. The average tumor weight (222.9 ± 116.9 mg) in mice treated with PBI-05204 (20 mg/kg) was significantly reduced from that in controls (920.0 ± 430.0 mg) (p < 0.05). Histopathologic examination of serial sections from each pancreas with no dissectible tumor in the PBI-05204 (40 mg/kg) treated group showed that the pancreatic tissues of 5/6 mice were normal while the remaining mouse had a tumor the largest diameter of which was less than 2.3 mm. In contrast, while gemcitabine alone did not significantly reduce tumor growth, PBI-05204 markedly enhanced the antitumor efficacy of gemcitabine in this particular model. Ki-67 staining was reduced in pancreatic tumors from mice treated with PBI-05204 (20 mg/kg) compared to that of control, suggesting that PBI-05204 inhibited the proliferation of the Panc-1 tumor cells. PBI-05204 suppressed expression of pAkt, pS6, and p4EPB1 in a concentration-dependent manner in both Panc-1 tumor tissues and human pancreatic cancer cell lines, implying that this novel botanical drug exerts its potent antitumor activity, at least in part, through down-regulation of PI3k/Akt and mTOR pathways.

Dynamic contrast-enhanced MRI for the detection of prostate cancer: meta-analysis.

OBJECTIVE: The purpose of this study was to systematically review and meta-analyze dynamic contrast-enhanced MRI (DCE-MRI) for the detection of prostate cancer in comparison with standard evaluation with T2-weighted imaging. MATERIALS AND METHODS: A PubMed electronic database search for the terms "dynamic contrast-enhanced," "prostate," and "MRI" was completed for articles up to September 17, 2013. All included studies had histopathologic correlation. Two by two contingency data were constructed for each study. A binormal bayesian ROC model was used to estimate and compare sensitivity, specificity, and AUC among eligible modalities. RESULTS: Both DCE-MRI (0.82-0.86) and diffusion-weighted MRI (DWI) (0.84-0.88) yielded significantly better AUC than T2-weighted imaging (0.68-0.77). Moreover, partial AUC for the combination of DCE-MRI, DWI, and T2-weighted imaging was improved significantly (0.111; 0.103-0.119) when compared with DCE-MRI alone (0.079; 0.072-0.085) and T2-weighted imaging alone (0.079; 0.074-0.084) but not DWI alone (0.099; 0.091-0.108). Sensitivity and specificity were similar among the four modalities. CONCLUSION: DCE-MRI improves AUC of tumor detection overall compared with T2-weighted imaging alone. Methods for DCE-MRI analysis require standardization, but visual analysis performs similar to semiquantitative methods. A two-parameter approach using DCE-MRI and T2-weighted imaging or DWI and T2-weighted imaging may be sufficient, and the latter may be more favorable for most routine prostate cancer imaging.

Diagnostic approach to hereditary renal cell carcinoma.

OBJECTIVE: The purpose of this article is to discuss the histopathologic features, genetics, clinical presentation, and imaging of hereditary renal cancer syndromes. CONCLUSION: Hereditary renal cell carcinoma syndromes can be diagnosed with a pattern-based approach focused on the predominant histologic renal cell carcinoma subtype and associated renal and extrarenal features of each syndrome.