Cardiac uptake patterns in routine 18F-FDG PET-CT scans: A pictorial review.

Broad variability of 18F-Fluoro-2-deoxyglucose (FDG) uptake is noted in myocardium while performing FDG PET-CT scans for viability, infection, or oncologic purposes. While most of the uptakes are considered non-specific, presence of underlying cardiac disease is seldom encountered. With this presentation, our intent is to pictorially highlight the variable FDG uptake patterns associated with the normal variations, benign, and malignant disease.

Vesicourachal Diverticulum: An Uncommon Incidental Finding on Staging 18F-FDG PET/CT in a Patient with Suspected Malignant Transformation of Neurofibromatosis.

In a 32-y-old man with neurofibromatosis type 1, 18F-FDG PET/CT incidentally revealed a vesicourachal diverticulum, a rare anatomic variant. The PET/CT, performed for staging a malignant peripheral nerve sheath tumor, highlighted a distinctive 18F-FDG-avid pattern crucial for accurate diagnosis. Recognizing such features enhances disease assessment and clarifies distinctions between benign urogenital anomalies and malignancies in 18F-FDG PET/CT staging.

Negative regulation of EGFR-Vav2 signaling axis by Cbl ubiquitin ligase controls EGF receptor-mediated epithelial cell adherens junction dynamics and cell migration.

The E3 ubiquitin ligase Casitas B lymphoma protein (Cbl) controls the ubiquitin-dependent degradation of EGF receptor (EGFR), but its role in regulating downstream signaling elements with which it associates and its impact on biological outcomes of EGFR signaling are less clear. Here, we demonstrate that stimulation of EGFR on human mammary epithelial cells disrupts adherens junctions (AJs) through Vav2 and Rac1/Cdc42 activation. In EGF-stimulated cells, Cbl regulates the levels of phosphorylated Vav2 thereby attenuating Rac1/Cdc42 activity. Knockdown of Cbl and Cbl-b enhanced the EGF-induced disruption of AJs and cell motility. Overexpression of constitutively active Vav2 activated Rac1/Cdc42 and reorganized junctional actin cytoskeleton; these effects were suppressed by WT Cbl and enhanced by a ubiquitin ligase-deficient Cbl mutant. Cbl forms a complex with phospho-EGFR and phospho-Vav2 and facilitates phospho-Vav2 ubiquitinylation. Cbl can also interact with Vav2 directly in a Cbl Tyr-700-dependent manner. A ubiquitin ligase-deficient Cbl mutant enhanced the morphological transformation of mammary epithelial cells induced by constitutively active Vav2; this effect requires an intact Cbl Tyr-700. These results indicate that Cbl ubiquitin ligase plays a critical role in the maintenance of AJs and suppression of cell migration through down-regulation of EGFR-Vav2 signaling.

Distinct roles for Rho versus Rac/Cdc42 GTPases downstream of Vav2 in regulating mammary epithelial acinar architecture.

Non-malignant mammary epithelial cells (MECs) undergo acinar morphogenesis in three-dimensional Matrigel culture, a trait that is lost upon oncogenic transformation. Rho GTPases are thought to play important roles in regulating epithelial cell-cell junctions, but their contributions to acinar morphogenesis remain unclear. Here we report that the activity of Rho GTPases is down-regulated in non-malignant MECs in three-dimensional culture with particular suppression of Rac1 and Cdc42. Inducible expression of a constitutively active form of Vav2, a Rho GTPase guanine nucleotide exchange factor activated by receptor tyrosine kinases, in three-dimensional MEC culture activated Rac1 and Cdc42; Vav2 induction from early stages of culture impaired acinar morphogenesis, and induction in preformed acini disrupted the pre-established acinar architecture and led to cellular outgrowths. Knockdown studies demonstrated that Rac1 and Cdc42 mediate the constitutively active Vav2 phenotype, whereas in contrast, RhoA knockdown intensified the Vav2-induced disruption of acini, leading to more aggressive cell outgrowth and branching morphogenesis. These results indicate that RhoA plays an antagonistic role to Rac1/Cdc42 in the control of mammary epithelial acinar morphogenesis.

A large pleural effusion in a patient receiving peritoneal dialysis.

Hydrothorax as a complication of peritoneal dialysis (PD) is a rare but recognized event. Proposed mechanisms for the development of a pleuro-peritoneal communication include congenital diaphragmatic defects, acquired weakening of diaphragmatic fibers caused by high intra-abdominal pressures during peritoneal dialysis, and impairments in lymphatic drainage. Pleural fluid analysis and diagnostic imaging assist in differentiation from other causes of pleural effusion. Nearly 50% of patients with this diagnosis have resolution of hydrothorax after temporary cessation of PD with interim hemodialysis for 2-6 weeks. Historically, other treatment options have included conventional pleurodesis and open thoracotomy with direct repair, producing variable results. With the advent of video-assisted thoracoscopy (VATS), surgical repairs and pleurodesis are now frequently performed under direct visualization with minimal invasiveness. We report a case of hydrothorax in a patient after recent introduction to peritoneal dialysis. Pleuro-peritoneal communication was documented with thoracentesis and radionuclide scanning. VATS pleurodesis with talc was performed. Repeat scintigraphy performed 1 week after the procedure revealed no residual communication, and patient was able to resume PD without further complications.

18F-FDG PET/CT Appearance of Plugoma.

Postsurgical anatomic alterations and placement of prosthetic materials may cause misdiagnosis, leading to unnecessary patient work-up. Reading physicians must be aware of common and uncommon postoperative imaging appearances and their pitfalls. In this case report, we present the appearance of a postsurgical hernia repair plug on PET/CT, also called plugoma or meshoma.

Development of a VX2 pancreatic cancer model in rabbits: a pilot study.

PURPOSE: An animal model of pancreatic cancer that is large enough to permit imaging and catheterization would be desirable for interventional radiologists to develop novel therapies for pancreatic cancer. The purpose of this study was to test the hypothesis that the VX2 rabbit model of pancreatic cancer could be developed as a suitable platform to test future interventional therapies. MATERIALS AND METHODS: The authors implanted and grew three pancreatic VX2 tumors per rabbit in six rabbits. Magnetic resonance (MR) imaging was performed at 2 weeks to confirm tumor growth. At 3 weeks, the authors selectively catheterized the gastroduodenal artery under guidance of x-ray digital subtraction angiography (DSA). T2-weighted anatomic imaging, diffusion-weighted MR imaging, and transcatheter intraarterial perfusion (TRIP) MR imaging were then performed. After imaging, tumors were confirmed at necropsy and histopathologically. Tumor sizes at 2 and 3 weeks were compared with a paired t test (P = .05). RESULTS: VX2 pancreatic tumors were grown in all six rabbits. The difference between tumor sizes at 2 and 3 weeks (1.29 cm +/- 0.39 vs 1.91 cm +/- 0.50, respectively) was significant (P < .001). All tumors were confirmed to be located within pancreatic tissue via histopathologic analysis. DSA and TRIP MR imaging were successful in five rabbits. Diffusion-weighted and anatomic MR imaging were successful in all six rabbits. CONCLUSIONS: The VX2 rabbit model of pancreatic cancer is feasible, as verified by imaging and pathologic correlation, and may be a suitable platform to test future interventional therapies.

68Gallium-DOTATATE positron emission tomography-computed tomography (PET CT) changes management in a majority of patients with neuroendocrine tumors.

BACKGROUND: 68Gallium-DOTATATE positron emission tomography-computed tomography (PET CT) has shown superior accuracy in detecting grade 1 and 2 neuroendocrine tumors over previous imaging modalities and was recently included in National Comprehensive Cancer Network guidelines. It remains unclear which patients benefit most from this imaging modality. We therefore reviewed our initial experience with 68Gallium-DOTATATE PET CT to evaluate its usefulness in diagnosing, staging, and surveilling neuroendocrine tumors. METHODS: Records of patients who underwent 68Gallium-DOTATATE PET CT from March to December 2017 were prospectively evaluated. The primary endpoint was whether 68Gallium-DOTATATE PET CT changes treatment in patients with neuroendocrine tumors. Descriptive statistics, Fisher exact tests, and nested logistic regressions were conducted. RESULTS: A total of 50 consecutive patients were included. Of these, 41 patients (82%) had a biopsy-proven neuroendocrine tumor at the time of imaging. The remaining 9 patients (18%) had symptoms or biochemistry suggestive of a neuroendocrine tumor with negative cross-sectional imaging. 68Gallium-DOTATATE PET CT changed management in 33 patients (66%). There were 24 patients with intermodality changes in management and 9 patients with intramodality changes in management. Patients with scans performed for staging had a higher likelihood of a change in management (P = .006). CONCLUSION: Performing 68Gallium-DOTATATE PET CT should be considered for staging and surveillance of neuroendocrine tumors because it is frequently associated with changes in management.

MR tracking of iron-labeled glass radioembolization microspheres during transcatheter delivery to rabbit VX2 liver tumors: feasibility study.

PURPOSE: To prospectively test the hypothesis that iron labeling of radioembolization microspheres permits their visualization by using magnetic resonance (MR) imaging for in vivo tracking during transcatheter delivery to liver tumors. MATERIALS AND METHODS: All experiments were approved by the Institutional Animal Care and Use Committee. Phantom studies were performed to quantify microsphere relaxivity and volume susceptibility properties and compare image contrast patterns resulting from aggregate deposition of unlabeled and iron-labeled microspheres. In seven rabbits in which nine VX2 liver tumors were implanted, T2*-weighted gradient-echo (GRE) MR images with negative image contrast (NC), white-marker (WM) GRE images with positive image contrast (PC), and on-resonance water-suppression turbo spin-echo (SE) images with PC were obtained before and after catheter-directed administration of microspheres into the hepatic artery. During each injection, serial GRE acquisitions were performed for real-time visualization of microsphere delivery. Contrast-to-noise ratios (CNRs) were measured between regions of microsphere accumulation and regions of normal liver parenchyma that demonstrated no apparent microsphere accumulation. Pre- and postinjection CNR measurements at identical spatial positions were compared by using paired t test (alpha = .05). RESULTS: Conventional microspheres did not produce detectable image contrast in phantoms. Iron-labeled microspheres produced susceptibility-induced dipole patterns with spatial extent of image contrast increasing with increasing microsphere dose. Real-time image series depicted both preferential delivery to tumor tissues and nontargeted delivery to adjacent organs. T2*-weighted GRE, WM GRE, and on-resonance water-suppression turbo SE each permitted in vivo visualization of the microsphere deposition, with postinjection CNR values (mean, 14.29 +/- 3.98 [standard deviation], 1.87 +/- 0.93, and 19.30 +/- 8.72, respectively) significantly greater than corresponding preinjection CNR values (mean, 2.02 +/- 4.65, 0.02 +/- 0.27, 0.85 +/- 2.65, respectively) (P < .05). CONCLUSION: Microsphere tracking during radioembolization may permit real-time verification of delivery and detection of extrahepatic shunting.

Four-dimensional transcatheter intraarterial perfusion (TRIP)-MRI for monitoring liver tumor embolization in VX2 rabbits.

Transcatheter intraarterial perfusion (TRIP)-MRI is an intraprocedural technique to iteratively monitor liver tumor perfusion changes during transcatheter arterial embolization (TAE) and chemoembolization (TACE). However, previous TRIP-MRI approaches using two-dimensional (2D) T(1)-weighted saturation-recovery gradient-recalled echo (GRE) sequences provided only limited spatial coverage and limited capacity for accurate perfusion quantification. In this preclinical study, a quantitative 4D TRIP-MRI technique (serial iterative 3D volumetric perfusion imaging) with rigorous radiofrequency (RF) B(1) field calibration and dynamic tissue longitudinal relaxation rate R(1) measurement is presented for monitoring intraprocedural liver tumor perfusion during TAE. 4D TRIP-MRI and TAE were performed in five rabbits with eight VX2 liver tumors (N = 8). After B(1) calibrated baseline and dynamic R(1) quantification, subsequent tissue contrast agent concentration time curves were derived. A single-input flow-limited pharmacokinetic model and peak gradient method were applied for perfusion analysis. The perfusion Frho reduced significantly from pre-TAE 0.477 (95% confidence interval [CI]: 0.384-0.570) to post-TAE 0.131 (95% CI: 0.080-0.183 ml/min/ml, P < 0.001).

Comparison of hypoxia-inducible factor-1alpha expression before and after transcatheter arterial embolization in rabbit VX2 liver tumors.

PURPOSE: To test the hypothesis that transcatheter arterial embolization (TAE) induces expression of hypoxia-inducible factor-1alpha (HIF-1alpha) within the same rabbit VX2 liver tumor. MATERIALS AND METHODS: Seven VX2 tumors were grown in the livers of five New Zealand white rabbits. Ultrasonography-guided biopsy was performed before and 10 minutes after TAE in all tumors. Pre- and post-TAE tumor biopsy specimens along with post-TAE whole liver tumor sections were stained with HIF-1alpha antibody and analyzed for percentage of HIF-1alpha-positive nuclei by using a spectral unmixing system mounted on a high-powered microscope. Statistical data comparisons were performed with the Wilcoxon signed-rank test (alpha = 0.05). RESULTS: TAE of liver tumors resulted in a statistically significant increase in the mean percentage of HIF-1alpha expression. The mean percentage of HIF-1alpha-positive stained nuclei increased from 23% +/- 3.5 in pre-TAE biopsy specimens to 41% +/- 8.7 in post-TAE biopsy specimens (P < .02). The increase was even more significant when the mean percentage of HIF-1alpha-positive stained nuclei from the same pre-TAE biopsy specimens was compared with sections from post-TAE whole tumor specimens (60% +/- 8.9, P < .02). CONCLUSIONS: The results of this study revealed that hypoxia caused by TAE of VX2 liver tumors activates HIF-1alpha, a transcription factor that in turn regulates other pro-angiogenic factors.

Intraprocedural diffusion-weighted PROPELLER MRI to guide percutaneous biopsy needle placement within rabbit VX2 liver tumors.

PURPOSE: To test the hypothesis that diffusion-weighted (DW)-PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) magnetic resonance imaging (MRI) can be used to guide biopsy needle placement during percutaneous interventional procedures to selectively target viable and necrotic tissues within VX2 rabbit liver tumors. MATERIALS AND METHODS: Our institutional Animal Care and Use Committee approved all experiments. In six rabbits implanted with 15 VX2 liver tumors, baseline DW-PROPELLER images acquired prior to the interventional procedure were used for apparent diffusion coefficient (ADC) measurements. Next, intraprocedural DW-PROPELLER scans were performed with needle position iteratively adjusted to target viable, necrotic, or intermediate border tissue regions. DW-PROPELLER ADC measurements at the selected needle tip locations were compared with the percentage of tumor necrosis qualitatively assessed at histopathology. RESULTS: DW-PROPELLER images demonstrated intratumoral tissue heterogeneity and clearly depicted the needle tip position within viable and necrotic tumor tissues. Mean ADC measurements within the region-of-interest encompassing the needle tip were highly correlated with histopathologic tumor necrotic tissue assessments. CONCLUSION: DW-PROPELLER is an effective method to selectively position the biopsy needle tip within viable and necrotic tumor tissues. The DW-PROPELLER method may offer an important complementary tool for functional guidance during MR-guided percutaneous procedures.

Diffusion-weighted PROPELLER MRI for quantitative assessment of liver tumor necrotic fraction and viable tumor volume in VX2 rabbits.

PURPOSE: To test the hypothesis that diffusion-weighted (DW)-PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) MRI provides more accurate liver tumor necrotic fraction (NF) and viable tumor volume (VTV) measurements than conventional DW-SE-EPI (spin echo echo-planar imaging) methods. MATERIALS AND METHODS: Our institutional Animal Care and Use Committee approved all experiments. In six rabbits implanted with 10 VX2 liver tumors, DW-PROPELLER and DW-SE-EPI scans were performed at contiguous axial slice positions covering each tumor volume. Apparent diffusion coefficient maps of each tumor were used to generate spatially resolved tumor viability maps for NF and VTV measurements. We compared NF, whole tumor volume (WTV), and VTV measurements to corresponding reference standard histological measurements based on correlation and concordance coefficients and the Bland-Altman analysis. RESULTS: DW-PROPELLER generally improved image quality with less distortion compared to DW-SE-EPI. DW-PROPELLER NF, WTV, and VTV measurements were strongly correlated and satisfactorily concordant with histological measurements. DW-SE-EPI NF measurements were weakly correlated and poorly concordant with histological measurements. Bland-Altman analysis demonstrated that DW-PROPELLER WTV and VTV measurements were less biased from histological measurements than the corresponding DW-SE-EPI measurements. CONCLUSION: DW-PROPELLER MRI can provide spatially resolved liver tumor viability maps for accurate NF and VTV measurements, superior to DW-SE-EPI approaches. DW-PROPELLER measurements may serve as a noninvasive surrogate for pathology, offering the potential for more accurate assessments of therapy response than conventional anatomic size measurements.

Comparison of two different methods for inoculating VX2 tumors in rabbit livers and hind limbs.

PURPOSE: To compare two methods to (a) propagate VX2 cell strain in rabbit hind limbs and (b) inoculate liver parenchymal tumors in rabbits. MATERIALS AND METHODS: One hundred forty-two New Zealand white rabbits were used for this study (60 with hind limb tumor [donors] and 82 with liver tumors [recipients]). In the donor group, nine rabbits received frozen VX2 cell suspension and 51 were injected with freshly prepared VX2 cell suspension. In the recipient group, 32 rabbits were injected with VX2 tumor cells and 50 were implanted with a small tumor fragment in the liver parenchyma. Success rates in terms of tumor growth were compared by using chi(2) or Fisher exact tests, with alpha = .05. RESULTS: Hind limb and liver tumors were successfully grown in 48 of the 60 rabbits in the donor group (80%) and 57 of the 82 rabbits in the recipient group (70%). The success rate of growing hind limb tumors increased from 33% (three of nine rabbits) to 88% (45 of 51 rabbits) when fresh VX2 cells instead of frozen were injected percutaneously (P < .0011). Similarly, the success rate for VX2 liver tumors almost doubled from 47% (15 of 32 rabbits) to 84% (42 of 50 rabbits) when a tumor fragment instead of VX2 cell suspension was used (P < .00036). This also significantly reduced the frequency of metastasis (P < .005). CONCLUSIONS: The authors recommend (a) the use of fresh VX2 cell suspension for percutaneous injection in the hind limbs of rabbits to maintain the VX2 cell strain and (b) the surgical implantation of freshly harvested VX2 tumor fragment into the liver parenchyma to establish liver tumors.

Effect of C-arm angiographic CT on transcatheter arterial chemoembolization of liver tumors.

Rotational C-arm angiographic computed tomography (CT) with a flat-panel radiography unit permits three-dimensional (3D) reconstruction of soft tissues and blood vessels. The usefulness of this C-arm technique during transcatheter arterial chemoembolization (TACE) is unknown. The authors analyzed the role of the C-arm technique in 18 patients with unresectable liver tumors during TACE. The technique altered the catheter position anticipated by attending interventional radiologists in seven of the 18 patients (39%; 95% confidence interval [CI]: 20%, 61%) and improved the diagnostic confidence in the selected catheter position in 14 of the 18 patients (78%; 95% CI: 55%, 91%). The technique provides CT-like images that are useful to interventional radiologists during TACE.