Contrast Washout Research Articles

Abstract A10: Unsupervised deconvolution of dynamic imaging reveals intratumor vascular heterogeneity and repopulation dynamics

Abstract Intratumor functional heterogeneity is the presence of multiple subpopulations or localized regions with different physiological properties that affect cancer biology (e.g., motility, invasion) and/or response to systemic therapy. Functional heterogeneity may reflect unique aspects of the tumor microenvironment or cellular genetic diversity including, but not limited to, the consequences of different localized patterns of vascular perfusion, stromal infiltration, somatic mutation, epigenetic modifications. Given the continuing improvements in tumor imaging technologies and the biological importance of tumor vascularization as a major driver of functional heterogeneity, the goal of the present work was to develop novel mathematical models to study vascular heterogeneity and its changes in tumors using data from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI provides a noninvasive in vivo method to evaluate tumor vasculature architectures based on contrast accumulation and washout. Understanding the role of vascular heterogeneity in tumors has significant implications for advancing individualized cancer diagnosis and treatment. To improve vascular characterization, we developed multi-tissue compartment modeling (MTCM). Notably, MTCM is a fully unsupervised method for deconvoluting dynamic imaging series data from heterogeneous tumors that contain unknown numbers of distinct vascular compartments. The pixel-wise tracer concentration in a particular vascular compartment is modeled as being proportional to the local volume transfer constant of the vascular compartment. However, the imaging data often contain significant numbers of partial-volume pixels. To address this limitation, MTCM estimates pharmacokinetic parameters (flux rate constants) using the time-courses of pure-volume pixels, i.e., the signals from those pixels highly enriched in a particular vascular compartment. A convex analysis of mixtures scheme is applied to identify those pure-volume pixels present at the vertices of the clustered pixel time series scatter simplex, without any knowledge of compartment distribution. Thus, MTCM offers an unsupervised approach to characterize intratumor heterogeneity. Applying MTCM to dynamic contrast-enhanced MRI of breast cancers revealed characteristic intratumor vascular heterogeneity and therapeutic responses that were otherwise undetectable. We identified differential and heterogeneous changes in tissue-specific vascular pharmacokinetics in tumors during treatment that were undetected using standard analysis, including tumor islands of persistent enhancement that have escaped the effects of therapy. While it is not yet possible to assign causality, these in vivo results allowed us to propose new hypotheses regarding the complex relationships between intratumor heterogeneity, clonal repopulation, cancer stem-cell, and therapeutic efficacy. Citation Format: Li Chen, peter Choyke, Robert Clarke, Zaver Bhujwalla, Yue Wang. Unsupervised deconvolution of dynamic imaging reveals intratumor vascular heterogeneity and repopulation dynamics. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A10. doi:10.1158/1538-7445.CHTME14-A10

Adrenal Leiomyoma Mimicking Adrenal Malignancy: Diagnostic Challenges and Review of Literature

Leiomyoma arising from adrenals are extremely rare with less than 20 cases reported in medical literature. Leiomyomas, though benign lesions, may frequently be confused with a malignancy, both clinically and on imaging studies, especially when they occur at atypical sites like the adrenals. We present a 42-year-old lady with cachetic symptoms, abdominal swelling and dragging sensation for 6 months, having a 10 cm diameter non-tender firm palpable abdominal mass, which on computed tomography was diagnosed to be a 12.2 × 10.3 × 8.0 cm heterogeneously enhancing adrenal mass having absolute and relative contrast washout values suggestive of malignancy. The tumor was hormonally inactive. Left adrenalectomy was done. Resected specimen weighed 91 g measuring 12 × 10 × 8.0 cm. Histopathology revealed a well-circumscribed and encapsulated benign spindle cell arranged in fascicles and whorls confirming leiomyoma. In the last evaluation 6 months after surgery, there was no evidence of tumor recurrence. This is the largest adrenal leiomyoma ever reported. Leiomyomas have a varied age of presentation (2 - 72 years, median: 38) with female preponderance. They are usually unilateral and hormonally inactive. Human immunodeficiency virus and Epstein-Barr virus infections have been observed in 44.44% and 16.67% of cases respectively. However, direct link between immunodeficiency and adrenal leiomyoma has not been established. Adrenal leiomyoma can present as huge abdominal masses clinically mimicking malignancy, and radiologic investigations can also be misleading. Adrenal leiomyoma should always be considered in the differential diagnosis of huge unilateral non-functional incidentally detected adrenal lesions. J Endocrinol Metab. 2015;5(5):304-308 doi: http://dx.doi.org/10.14740/jem318w

Delayed uptake and washout of contrast in non-viable infarcted myocardium shown with dynamic computed tomography.

Assessment of ischemic but potentially viable myocardium plays an important role in the planning of coronary revascularization. Until now SPECT, PET, and MRI have been used to identify viable myocardium. Computed tomography (CT) is increasingly used to diagnose coronary atherosclerosis. To evaluate the feasibility of CT enhancement as a viability marker by investigating myocardial contrast distribution over time in pigs with experimentally induced antero-septal myocardial infarctions. Twelve pigs were subjected to 60 min of balloon occlusion of the left anterior descending artery, followed by removal of the balloon and reperfusion. Four pigs died due to refractory ventricular fibrillation. After 6 weeks, dynamic cardiac CT was performed assessing both wall motion and contrast attenuation. Measurements of attenuation values in Hounsfield units (HU) in the infarct zone and the normal lateral wall were performed at 20 s, and 1, 3, 5, 8 and 12 min after contrast injection. We found highly significant differences in attenuation values between the two zones at all-time points except t =1 min (ANOVA P=0.85). The normal myocardium showed higher uptake- and washout-rates of contrast than the infarct zone (84±15 vs. 58±8 at 20 s, P=0.0001 and 27±12 vs. 81±13 at 12 min, P=0.0001). Specifically, the ratio between early (20 s) and late (12 min) uptake is a valid marker of viable myocardium. In all animals this ration was above one in the normal zone and below one in the infarct zone. Delayed infarct related uptake and washout of contrast shows promise for future clinical application of CT in a combined assessment of coronary atherosclerosis and myocardial viability.

Dynamic contrast-enhanced ultrasound (DCE-US) for the characterization of hepatocellular carcinoma and cholangiocellular carcinoma.

In a prospective study, we compared the different perfusion kinetics of HCC and ICC using dynamic contrast-enhanced ultrasound (DCE-US). Patients with proven HCC and ICC were included. Three-minute video clips of CEUS examinations (CPS - low MI mode) after a bolus injection of 1.2 ml SonoVue were recorded and analyzed with quantification software (VueBox). Parameters for the arterial contrast enhancement [rise time (RT), time-to-peak (TTP)] towards portal venous contrast enhancement [mean transit time (local) (mTTl) and fall time (FT)] were quantified. Furthermore, contrast wash-out after peak enhancement (PE) (40 s, 80 s, 100 s and 120 s after PE) was compared between HCC and ICC. 43 patients with proven HCC (n = 23 HCC; cirrhosis n = 16) and ICC (n = 20 ICC; Cirrhosis n = 6) were examined. No statistical difference of the arterial DCEUS parameters was found between HCC and ICC. Contrast enhancement of the portal venous and late phases showed significantly lower values in the ICC group indicating early wash-out of the contrast agent: mTTl (p = 0.0209): HCC 118.4 s (SD± 88.4); ICC 64.8 s (SD± 49.7). FT (p = 0.0433): HCC 42.5 s (SD± 27.7); ICC 27.7 s (SD± 16.2). The percental loss of intensity at a definite time point after PE was significantly higher in ICC than in HCC lesions. DCE-US is able to detect and quantify differences in perfusion kinetics between HCC and ICC. Whereas arterial contrast enhancement patterns may overlap between HCC and ICC, a timed characterization of wash-out kinetics may offer an additional tool to characterize HCC and ICC. The presence of a rapid loss of signal intensity in the early portal venous phase is significantly higher in ICC than in HCC lesions.

The association between muscle perfusion assessed by dynamic contrast enhanced magnetic resonance imaging and knee related pain and function in patients with knee osteoarthritis: an exploratory cross sectional study

The association between muscle perfusion assessed by dynamic contrast enhanced magnetic resonance imaging and knee related pain and function in patients with knee osteoarthritis: an exploratory cross sectional study

Stereotactic Body Radiotherapy-Induced Arterial Hypervascularity of Non-Tumorous Hepatic Parenchyma in Patients with Hepatocellular Carcinoma: Potential Pitfalls in Tumor Response Evaluation on Multiphase Computed Tomography

PurposeTo evaluate temporal changes in contrast enhancement patterns of non-tumorous hepatic parenchyma with a focus on arterial hypervascularity on multiphase computed tomography (CT) in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT).MethodsWe retrospectively identified 61 patients who had undergone multiphase contrast-enhanced CT at one, three, and six months after SBRT. Irradiated versus non-irradiated liver parenchyma was delineated by cross-correlation with the dose-volume histogram of SBRT plan. Serial changes in the contrast enhancement patterns of the irradiated versus non-irradiated liver parenchyma were evaluated by two abdominal radiologists in consensus. We compared the frequency of the contrast enhancement patterns according to the follow-up period using the Fisher-Freeman-Halton exact test.ResultsThe irradiated non-tumorous hepatic parenchyma showed that the prevalence of arterial hypervascularity increased during the follow-up period (P<.01): 11.5% (7/61) in one, 45.9% (28/61) in three, and 54.1% (33/61) in six months. Contrast wash-out on the delayed phase was uncommon: 1.6% (1/61) in one, 3.3% (2/61) in three, and 0% in six months.ConclusionThe incidence of arterial hypervascularity of the irradiated hepatic parenchyma gradually increased until six months after SBRT, which could interfere with the accurate evaluation of treatment response. The lack of wash-out on the delayed phase in the hypervascular area would distinguish SBRT-related change from residual/recurred HCC.

Adrenal disease: a clinical update and overview of imaging. A review

The aim of this article is to provide an overview of the most frequent clinically significant adrenal diseases and to describe the latest trends in their diagnostics, particularly by means of imaging techniques. The authors reviewed standard textbooks and subsequently conducted a search using the PubMed (Public/Publisher MEDLINE) electronic database by the year 2013 with the following search terms: adrenal masses, adrenal adenoma, phaeochromocytoma, adrenocortical carcinoma, metastases, incidentalomas, hypercortisolism, hyperaldosteronism. If adrenal disease is clinically suspected, hormone tests are performed to detect adrenal hyperfunction and imaging studies are used to assess the nature of adrenal lesion. The most frequent syndromes include hypercortisolism, primary hyperaldosteronism, and phaeochromocytoma. The clinically most significant pathologies of the adrenal glands are adenomas and adrenal hyperplasia, adrenocortical carcinomas, phaeochromocytomas, and metastases. Given the availability and improved quality of imaging techniques, adrenal incidentalomas are detected increasingly often. In these cases, it is necessary to rule out hormonal activity and malignancy. Incidentalomas can be associated with clinical syndromes of adrenal hormone overproduction. In most cases, they are clinically silent. In some cases, the definitive diagnosis can be determined as early as during the initial examination with an imaging technique (most frequently, a CT scan). If the finding is inconsistent, other imaging techniques can be used: CT contrast washout analysis, MRI, SPECT or PET/CT. In the case of adrenal gland disorders, correct interpretation of the results of laboratory tests and imaging studies is essential for further management of these patients.

Normalized gradient fields for nonlinear motion correction of DCE-MRI time series

Dynamic MR image recordings (DCE-MRI) of moving organs using bolus injections create two different types of dynamics in the images: (i) spatial motion artifacts due to patient movements, breathing and physiological pulsations that we want to counteract and (ii) signal intensity changes during contrast agent wash-in and wash-out that we want to preserve. Proper image registration is needed to counteract the motion artifacts and for a reliable assessment of physiological parameters. In this work we present a partial differential equation-based method for deformable multimodal image registration using normalized gradients and the Fourier transform to solve the Euler–Lagrange equations in a multilevel hierarchy. This approach is particularly well suited to handle the motion challenges in DCE-MRI time series, being validated on ten DCE-MRI datasets from the moving kidney. We found that both normalized gradients and mutual information work as high-performing cost functionals for motion correction of this type of data. Furthermore, we demonstrated that normalized gradients have improved performance compared to mutual information as assessed by several performance measures. We conclude that normalized gradients can be a viable alternative to mutual information regarding registration accuracy, and with promising clinical applications to DCE-MRI recordings from moving organs.

CT imaging characteristics of oncocytic adrenal neoplasms (OANs): comparison with adrenocortical carcinomas

Oncocytic adrenal neoplasms (OANs) are rare, but are an important subtype of adrenal tumors that is being diagnosed with increasing frequency. Unfortunately, the imaging characteristics of this tumor have not been well described. Our purpose was to identify CT features to differentiate OANs from adrenocortical carcinomas (ACC). From 1991 to 2012, 18 patients with OANs were identified from our institution's pathology database. Twelve had CT examinations available for review. CT characteristics of five benign and seven malignant OANs were reviewed by two abdominal radiologists, and compared to ACC (n=10). Morphologic characteristics and density measurements were recorded for each imaging phase. Absolute contrast washout was calculated and compared. Benign OANs were smaller [meansize 3.7cm (range 2.6-5.3)] and more homogeneous than malignant OANs and demonstrated greater washout [mean washout percentage 72.3% (range 61-88)]. Malignant OANs demonstrated features similar to ACCs, including size [mean 9.4cm (range 5.2-9.8)] and internal necrosis (n=6). Mean enhancement washout percentage for malignant OANs was 12% (range -8 to 32). Benign OANs (oncocytomas) may be distinguished from lipid-rich adenomas on non-contrast CT but may be indistinguishable from lipid-poor adenomas. Malignant oncocytic neoplasms can demonstrate features similar to ACCs, including larger size, internal necrosis, and lower percentage enhancement washout.

A simple and inexpensive system for controlling body temperature in small animal experiments using MRI and the effect of body temperature on the hepatic kinetics of Gd-EOB-DTPA

The purpose of this study was to develop a simple and inexpensive system for controlling body temperature in small animal experiments using magnetic resonance imaging (MRI) and to investigate the effect of body temperature on the kinetic behavior of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) in the liver.In our temperature-control system, body temperature was controlled using a feedback-regulated heated or cooled air flow generated by two Futon dryers. The switches of the two Futon dryers were controlled using a digital temperature controller, in which the rectal temperature of a mouse measured by an optical fiber thermometer was used as the input.In experimental studies, male ICR mice aged 8weeks old were used and allocated into 5 groups (39-, 36-, 33-, 30-, and 27-degree groups, n=10), in which the body temperature was maintained at 39 °C, 36 °C, 33 °C, 30 °C, and 27 °C, respectively, using our system. The dynamic contrast-enhanced MRI (DCE-MRI) data were acquired with an MRI system for animal experiments equipped with a 1.5-Tesla permanent magnet, for approximately 43min, after the injection of Gd-EOB-DTPA into the tail vein. After correction of the image shift due to the temperature-dependent drift of the Larmor frequency using the gradient-based image registration method with robust estimation of displacement parameters, the kinetic behavior of Gd-EOB-DTPA was analyzed using an empirical mathematical model. With the use of this approach, the upper limit of the relative enhancement (A), the rates of contrast uptake (α) and washout (β), the parameter related to the slope of early uptake (q), the area under the curve (AUC), the maximum relative enhancement (REmax), the time to REmax (Tmax), and the elimination half-life of the contrast agent (T1/2) were calculated.The body temperature of mice could be controlled well by use of our system. Although there were no significant differences in α, AUC, and q among groups, there were significant differences in A, REmax, β, Tmax, and T1/2, indicating that body temperature significantly affects the kinetic behavior of Gd-EOB-DTPA in the liver.In conclusion, our system will be useful for controlling body temperature in small animal experiments using MRI. Because body temperature significantly affects the kinetic behavior of Gd-EOB-DTPA in the liver, the control of body temperature is essential and should be carefully considered when performing DCE-MRI studies in small animal experiments.

Adrenal lesions: variability in attenuation over time, between scanners, and between observers

Measurements of attenuation (in Hounsfield units [HU]) and contrast wash-out are widely used to characterize adrenal lesions as benign or indeterminate/malignant at computed tomography (CT). Clinical experience suggests that such measurements of adrenal lesions may vary over time and between observers, making evaluation difficult. To investigate the change over time of adrenal lesion size, attenuation, and contrast wash-out at CT, to determine inter-observer variability, and to analyze other factors underlying the variability. In a cohort of patients, with or without malignant disease, undergoing CT, adrenal lesions were prospectively analyzed. Lesions with growth >20% or >5 mm over 6 months were excluded. Non-enhanced attenuation and contrast medium wash-out over 2-year follow-up were analyzed. An inter-observer analysis with five observers and a phantom study of eight different CT scanners were performed to assess measurement variability. Mean adrenal lesion non-enhanced attenuation values decreased by 0.5 HU/year during follow-up. Using 10 HU or 40% relative wash-out as threshold values for benign versus indeterminate lesions, 27 (20%) and 39 (29%) of 136 lesions, respectively, would be reclassified at some occasion during follow-up. In the observer analysis 37 of 40 lesions demonstrated agreement between all observers, using established threshold values. The phantom study showed an intra-scanner variability of 1-3 HU, but an inter-scanner variability of up to 8 HU for water. The clinically widespread use of specific attenuation threshold values for characterizing adrenal lesions must be used with great caution, considering that multiple factors, related to patient, equipment, scanning technique, and observer influence the outcome.

Long common bile duct stricture: Wait, are we on the right track?

Editor, Perforations during endoscopic retrograde cholangiopancreatography (ERCP) are rare. Risk factors include sphincterotomy, sphincter of Oddi dysfunction (SOD), dilated common bile duct (CBD), procedure duration, and stricture dilatation [1]. CBD perforation is very rare, and usually the lower part is involved [2]. We highlight difficulties in recognition through a case we encountered recently. A 67-year-old male with a past history of biliary pancreatitis and cholecystectomy presented with recurrent abdominal pain. Investigations revealed elevated serum alkaline phosphatase and a dilated (diameter 13 mm) CBD. At ERCP, cannulation was difficult and took 17.5 min. There was resistance at the lower CBD which disappeared, and the guide wire appeared to have reached the hepatic duct. However, there was poor filling of the bile duct with contrast (Fig. 1a), which was initially thought to be due to a long biliary stricture. Sphincterotomy and plastic stenting were done. However, blood was seen coming through the stent lumen as well as by the side of the stent. In view of suspected vascular injury, the stent was removed, and the bleeding stopped. Repeat cannulation was performed, and this time, adequate contrast filling was achieved. The cholangiogram revealed a dilated and slightly tortuous CBD (Fig. 1b).We assumed SOD, and sphincterotomy was completed followed by stenting. Bile flow was achieved. No postprocedural complications were noted. Retrospectively, when we compared the course of the guide wires (arrow in Fig. 1a, b), it appears that in the initial attempt, the CBD wall was dissected, and the contrast was tracking along the CBD wall. With the self-limiting bleed seen after initial cannulation attempt and absence of rapid washout of contrast, puncture of vascular structure is unlikely. Unfortunately, CT scan or MR imaging was not performed to confirm the dissection of the CBD wall. We conclude that CBD wall dissection along its length may occur during cannulation, giving a false appearance of CBD stricture on the cholangiogram. One should consider such a possibility when there is poor filling of the CBD lumen on the cholangiogram, especially after a prolonged and difficult cannulation attempt.

Delayed uptake and washout of contrast in non-viable infarcted myocardium - viability shown with 4D computer tomography

Delayed uptake and washout of contrast in non-viable infarcted myocardium - viability shown with 4D computer tomography

Quantitative image feedback in TACE-combining novel imageable beads and spectral CT

Purpose Currently, drug-eluting beads (DEB) are mixed with contrast medium and delivered together for transcatheter arterial chemoembolization (TACE). The mixture is imaged using conventional X-ray (fluoroscopy, DSA, and CBCT) to visualize DEBs deposition. However, given the fluid dynamic properties are different for the two materials (i.e. solid vs. liquid, different densities, etc.), they can separate and lead to incomplete/limited feedback of true DEB location during TACE; especially after contrast washout. Recently, imageable microspheres have been developed. While this has provided an added level of x-ray visibility, work also has been done to improve the x-ray imaging device. The purpose of this study is to show imageable bead visibility using energy-resolved CT, an emerging x-ray imaging modality allowing for material specific and quantitative imaging of contrast media [1]. Materials and Methods In a phantom study, imageable microspheres (0.1-0.3 mm) loaded with iodine containing lipiodol were embedded in agarose and scanned along with a phantom comprising distilled water and a probe filled with NaI (200 mm) as reference. Data were acquired using a spectral CT animal scanner prototype (Philips Research, Hamburg, Germany) equipped with a photon-counting detector. For comparison, conventional CT images were acquired. Results The iodine content in the microspheres showed inherent enhancement over background signal levels in the conventional CT images (CNRiodine/water=8.5). Using the spectral CT scanner and dedicated signal processing techniques, iodine maps with complete background suppression (CNRwater/air=0.08) were generated, providing a quantitative and protocol-independent measure of iodine concentration (i.e. mg/ml). Conclusion Combining imageable microspheres with the K-edge imaging capability of spectral CT allows for quantitative image feedback of administered beads. This example illustrates the importance of developing microspheres and imaging equipment that is optimized to work together and improve overall x-ray visibility.

Melanotic schwannoma of adrenal gland – A rare entity/diagnostic dilemma

Introduction and objectiveMelanotic schwannoma of adrenal gland is very rare entity with only two series and less than 100 cases reported in literature. We report a case of melanotic schwannoma. Case reportA 62 years old man, a resident of Tanzania presented with 6 months history of lower urinary tract symptoms (LUTS) for which he was evaluated and a right adrenal mass detected incidentally on ultrasound.He is known case of hypertension and hypothyroidism for which he is taking regular medications. On general examination pulse was 80/min, regular and BP was130/80 mm of Hg. Abdominal examination was unremarkable. MDCT examination revealed a right adrenal mass (4 × 4.8 cm) showing mild enhancement post contrast study with central area of relatively less enhancement showing no significant contrast washout on delayed study. The provisional diagnosis was ? pheochromocytoma, ? malignant. Functional study was found to be normal. Laparoscopic exploration was done and mass excised. Gross pathological examination showed a single globular circumscribed soft tissue mass measuring 4.5 × 4 × 3 cm and weighing 50 g with a nodular surface. The cut surface was black with a central golden brown area measuring around 2.2 × 1.8 cm.A diagnosis of malignant melanoma was considered, however in view of circumscription bland nuclei, absent of nucleoli, very few mitoses and presence of nerve fascicles; a diagnosis of melanotic schwannoma was favored. The patient was advised regular follow-up. ConclusionMelanotic schwannoma of adrenal is a very rare entity and every effort should be made to rule out melanoma.

Adrenal Masses

Adrenal masses are among the most common incidentally discovered lesions on cross-sectional imaging with estimated incidence of approximately 5%. In addition, adrenal lesions can also be detected as part of an endocrinology workup with suspicion of a functional adrenal mass. Regardless of the source of detection, it is crucial to differentiate a benign from a malignant process and furthermore utilize characteristic imaging appearance of different adrenal masses to facilitate diagnosis and guide management. There are numerous imaging protocols and postprocessing methods for evaluation of adrenal masses with high sensitivity and specificity with small differences between institutions. Currently, the most widely used imaging modality for evaluation of adrenal mass is computed tomography without and with contrast washout assessment. In this article, we review diagnostic approaches to adrenal masses using computed tomography and magnetic resonance imaging techniques and present imaging strategies utilized at our institution. The advantages and challenges of these imaging modalities for evaluation of adrenal pathologies are discussed.

Mapping Tumor Hypoxia In Vivo Using Pattern Recognition of Dynamic Contrast-enhanced MRI Data

In solid tumors, hypoxia contributes significantly to radiation and chemotherapy resistance and to poor outcomes. The “gold standard” pO2 electrode measurements of hypoxia in vivo are unsatisfactory because they are invasive and have limited spatial coverage. Here, we present an approach to identify areas of tumor hypoxia using the signal versus time curves of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data as a surrogate marker of hypoxia. We apply an unsupervised pattern recognition (PR) technique to determine the differential signal versus time curves associated with different tumor microenvironmental characteristics in DCE-MRI data of a preclinical cancer model. Well-perfused tumor areas are identified by rapid contrast uptake followed by rapid washout; hypoxic areas, which are regions of reduced vascularization, are identified by delayed contrast signal buildup and washout; and necrotic areas exhibit slow or no contrast uptake and no discernible washout over the experimental observation. The strength of the PR concept is that it captures the pixel-enhancing behavior in its entirety—during both contrast agent uptake and washout—and thus, subtleties in the temporal behavior of contrast enhancement related to features of the tumor microenvironment (driven by vascular changes) may be detected. The assignment of the tumor compartments/microenvironment to well vascularized, hypoxic, and necrotic is validated by comparison to data previously obtained using complementary imaging modalities. The proposed novel analysis approach has the advantage that it can be readily translated to the clinic, as DCE-MRI is used routinely for the identification of tumors in patients, is widely available, and easily implemented on any clinical magnet.

Comparison between PUN and Tofts models in the quantification of dynamic contrast-enhanced MR imaging

Dynamic contrast-enhanced study in magnetic resonance imaging (DCE-MRI) is an important tool in oncology to visualize tissues vascularization and to define tumour aggressiveness on the basis of an altered perfusion and permeability. Pharmacokinetic models are generally used to extract hemodynamic parameters, providing a quantitative description of the contrast uptake and wash-out. Empirical functions can also be used to fit experimental data without the need of any assumption about tumour physiology, as in pharmacokinetic models, increasing their diagnostic utility, in particular when automatic diagnosis systems are implemented on the basis of an MRI multi-parametric approach. Phenomenological universalities (PUN) represent a novel tool for experimental research and offer a simple and systematic method to represent a set of data independent of the application field. DCE-MRI acquisitions can thus be advantageously evaluated by the extended PUN class, providing a convenient diagnostic tool to analyse functional studies, adding a new set of features for the classification of malignant and benign lesions in computer aided detection systems. In this work the Tofts pharmacokinetic model and the class EU1 generated by the PUN description were compared in the study of DCE-MRI of the prostate, evaluating complexity of model implementation, goodness of fitting results, classification performances and computational cost. The mean R2 obtained with the EU1 and Tofts model were equal to 0.96 and 0.90, respectively, and the classification performances achieved by the EU1 model and the Tofts implementation discriminated malignant from benign tissues with an area under the receiver operating characteristic curve equal to 0.92 and 0.91, respectively. Furthermore, the EU1 model has a simpler functional form which reduces implementation complexity and computational time, requiring 6 min to complete a patient elaboration process, instead of 8 min needed for the Tofts model analysis.

Contrast-Enhanced Ultrasound in the Diagnosis of Gallbladder Diseases: A Multi-Center Experience

ObjectiveTo assess the usefulness of contrast–enhanced ultrasound (CEUS) in differentiating malignant from benign gallbladder (GB) diseases.MethodsThis study had institutional review board approval. 192 patients with GB diseases from 9 university hospitals were studied. After intravenous bonus injection of a phospholipid-stabilized shell microbubble contrast agent, lesions were scanned with low acoustic power CEUS. A multiple logistic regression analysis was performed to identify diagnostic clues from 17 independent variables that enabled differentiation between malignant and benign GB diseases. Receiver operating characteristic (ROC) curve analysis was performed.ResultsAmong the 17 independent variables, multiple logistic regression analysis showed that the following 4 independent variables were associated with the benign nature of the GB diseases, including the patient age, intralesional blood vessel depicted on CEUS, contrast washout time, and wall intactness depicted on CEUS (all P<0.05). ROC analysis showed that the patient age, intralesional vessels on CEUS, and the intactness of the GB wall depicted on CEUS yielded an area under the ROC curve (Az) greater than 0.8 in each and Az for the combination of the 4 significant independent variables was 0.915 [95% confidence interval (CI): 0.857–0.974]. The corresponding Az, sensitivity, and specificity for the age were 0.805 (95% CI: 0.746–0.863), 92.2%%, and 59.6%; for the intralesional vessels on CEUS were 0.813 (95% CI: 0.751–0.875), 59.8%, and 98.0%; and for the GB wall intactness were 0.857 (95% CI: 0.786–0.928), 78.4%, and 92.9%. The cut-off values for benign GB diseases were patient age <53.5 yrs, dotted intralesional vessels on CEUS and intact GB wall on CEUS.ConclusionCEUS is valuable in differentiating malignant from benign GB diseases. Branched or linear intralesional vessels and destruction of GB wall on CEUS are the CEUS features highly suggestive of GB malignancy and the patient age >53.5 yrs is also a clue for GB malignancy.

IMAGING DIAGNOSIS—CHOLANGIOCELLULAR ADENOMA: CONTRAST‐ENHANCED ULTRASONOGRAPHIC FINDINGS OF A BENIGN TUMOR MIMICKING MALIGNANT NEOPLASIA IN A DOG

A 9-year-old Giant Schnauzer was referred for polyuria and polydipsia. On abdominal ultrasound, a hyperechoic mass with low color Doppler signal was detected in the medial right hepatic lobe. Contrast-enhanced ultrasound (CEUS) demonstrated increased enhancement of the mass during the arterial phase, and contrast washout during portal and late phases with decreased enhancement relative to the liver. These findings were consistent with primary liver malignancy or liver metastasis. A final diagnosis of cholangiocellular adenoma was made based on histopathology. To our knowledge, this is the first description of a benign hepatic neoplasm exhibiting malignant CEUS characteristics in a dog.