Wash-in Rate Research Articles

Utility of contrast-enhanced ultrasound for solid mass surveillance and characterization in children with tuberous sclerosis complex: an initial experience.

Patients with tuberous sclerosis complex (TSC) can develop solid kidney masses from childhood. Imaging surveillance is done to detect renal cell carcinoma (RCC) and angiomyolipomas (AML), including AMLs at risk for hemorrhage. Intravenous contrast-enhanced ultrasound (CEUS) may be useful for screening as ultrasound is well tolerated by children and ultrasound contrast agents (UCA) are not nephrotoxic. Retrospective review of kidney CEUS exams of pediatric TSC patients. Qualitative CEUS analysis by consensus of 3 radiologists assessed rate, intensity, and pattern of lesion enhancement. Quantitative CEUS analysis was performed using Vuebox®. Where available, abdominal MRI was analyzed qualitatively for the same features and quantitatively by in-house-developed software. Time-intensity curves were generated from both CEUS and MRI where possible. Appearance of lesions were compared between CEUS and MRI and histology where available. Nine masses in 5 patients included one histologically proven RCC and 8 AMLs diagnosed by imaging. Quantitative CEUS of RCC showed malignant features including increased peak enhancement 162%, rapid wash-in rate 162%, and elevated washout rate 156% compared to normal kidney tissue; versus AML which was 68%, 105%, and 125%, respectively. All masses were hypoenhancing on MRI compared to normal kidney tissue; MR dynamic contrast study offered no distinction between RCC and AML. The only MRI feature differentiating RCC from AML was absence of fat. Temporal resolution afforded by CEUS was useful to distinguish malignant from benign kidney masses. CEUS may prove useful for screening, characterizing, and follow-up of kidney lesions in pediatric TSC patients.

Diagnostic performance of contrast-enhanced dynamic and diffusion-weighted MR imaging in the assessment of tumor response to neoadjuvant therapy in muscle-invasive bladder cancer.

To evaluate the diagnostic performance of DCE MRI and DWI in the assessment of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC). This prospective study included 90 patients with MIBC who finished NAC. Two radiologists independently assessed MRI for the determination of semi-quantitative parameters (wash-in rate and wash-out rate) and apparent diffusion coefficient (ADC) value. The correlation between pCR and wash-in rate, wash-out rate, ADC value were analyzed. The area under the ROC curve (AUC) was used to evaluate the diagnostic performance for detecting pCR. Inter-reader agreement was assessed using the ICC statistics. On cystectomy specimens, pCR was confirmed in (43.3%, 39/90). pCR is negatively correlated with wash-out rate (r = - 0.701, p = 0.01) and ADC value (r = - 0.621, p = 0.01). ADC value is positively correlated with wash-out rate (r = 0.631, p = 0.001). The diagnostic accuracy of ADC value (cut-off value: 0.911 × 10-3mm2/s) and wash-out rate (cut-off value: 0.677 min-1) in the identification of pCR was (92% for reader 1, 91% for reader 2), and (90% for reader 1, 88% for reader 2), respectively. The sensitivity, specificity for predicting pCR using ADC value + washout rate cut off values were 95.4%, 97.7% for reader 1, and 96%, 97% for reader 2, respectively. AUC was 0.981 for reader 1, 0.971 for reader 2. The overall reproducibility of the mean ADC value and wash out rate was excellent (ICC = 0.83-0.90). The ICC values for the mean ADC value, washout rate was 0.89 (95% CI 0.84-0.89) and 0.87 (95% CI 0.86-0.91), respectively. Semi-quantitative parameter (wash-out) derived from DCE-MRI and ADC has the potential to assess the tumor's complete pathologic response. The two parameters using together can offer the best possibility to identify complete response to NAC in MIBC.

Potential application of dynamic contrast enhanced ultrasound in predicting microvascular invasion of hepatocellular carcinoma.

To investigate the clinical value of dynamic contrast enhanced ultrasound (D-CEUS) in predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC). In this retrospective study, 16 patients with surgery and histopathologically proved HCC lesions were included. Patients were classified according to the presence of MVI: MVI positive group (n = 6) and MVI negative group (n = 10). Contrast enhanced ultrasound (CEUS) examinations were performed within a week before surgery. Dynamic analysis was performed by VueBox® software (Bracco, Italy). Three regions of interests (ROIs) were set in the center of HCC lesions, at the margin of HCC lesions and in the surrounding liver parenchyma accordingly. Time intensity curves (TICs) were generated and quantitative perfusion parameters including WiR (wash-in rate), WoR (wash-out rate), WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve) and WiPi (wash-in perfusion index) were obtained and analyzed. All of HCC lesions showed arterial hyperenhancement (100 %) and at the late phase as hypoenhancement (75%) in CEUS. Among all CEUS quantitative parameters, the WiAUC and WoAUC were higher in MVI positive group than in MVI negative group in the center HCC lesions (P < 0.05), WiAUC, WoAUC and WiPI were higher in MVI positive group than in MVI negative group at the margin of HCC lesions. WiR and WoR were significant higher in MVI positive group. D-CEUS with quantitative perfusion analysis has potential clinical value in predicting the existence of MVI in HCC lesions.

DCE-MRI for Detection of Acute Myeloid Leukemia Derived Bone Marrow Vascular Dysfunction

Acute Myeloid Leukemia (AML) is the most common acute leukemia in adults. While the clinical presentation is quite uniform, it is a highly heterogeneous disease at the genetic level. Using intravital two-photon microscopy in AML xenograft models, we have previously showed that AML patient-derived samples induced a common pathologic bone marrow (BM) vascular phenotype. To understand the translational potential of our findings we have optimized dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for the assessment of BM vascular dysfunction. We quantified non-model based parameters from DCE-MRI scans: Contrast Enhancement (CE); Wash-in Rate (WiR); and Wash-out Rate (WoR). CE reflects tissue vascular density and is a measurement of the proportion of fully functional vessels per pixel area, WIR reflects blood flow and tissue perfusion, and WoR reflects vascular permeability and tissue clearance capacity. We first measured DCE parameters in control mice. We observed no gender-related differences in BM DCE parameters, while we found significant age-related changes. As mice age, BM vascular density decreases together with increased vascular permeability and reduced tissue clearance capacity. When compared to age- matched controls, mice injected with AML cell lines showed decreased vascular density, decreased blood inflow, increased vascular permeability and reduced tissue clearance capacity. There was a progressive decline in BM vascular function as the disease burden increased, particularly in WiR and WoR parameters, with even low levels of leukemia significantly altering BM vascular function. When analyzing mice injected with AML patient samples, changes in BM vascular function were more dependent on the AML sample than on the engraftment. Low disease burden did not significantly change DCE vascular parameters. At high disease burden, patient-derived xenografts show different degrees of vascular disruption, spanning from global altered DCE parameters to milder phenotypes. Upon AraC treatment, altered vascular parameters remained unchanged in most of the cases, suggesting inability to fully rescue BM vascular function. In conclusion, we showed that DCE-MRI is able to detect consistent changes associated with BM vasculature induced by aging and leukemia. Despite the heterogeneous nature of the disease, our method captures different degrees of vascular alterations, with WIR having the highest diagnostic potential. Our results further suggest that the detection of a pathologic vascular phenotype in the BM of AML patients could be of use in the clinical scenario. Disclosures No relevant conflicts of interest to declare.

Characteristics of pleomorphic adenomas, adenolymphomas, and malignant tumors of the salivary glands on color doppler ultrasonography and contrast enhanced ultrasonography.

To provide a comprehensive description of the quantitative and qualitative characteristics of pleomorphic adenomas, adenolymphomas, and malignant tumors of the salivary glands on color doppler ultrasonography and contrast-enhanced ultrasonography (CEUS). 64 patients with 35 pleomorphic adenomas, 24 adenolymphomas, and 12 malignant tumors were enrolled in this study. All patients were examined by color doppler ultrasonography and CEUS before operation. In color Doppler ultrasonography, degree of vascularity, peak systolic velocity (PSV) and the vascular resistance index (RI) were obtained. In CEUS, type of enhancement, rim enhancement and area of enhancement were assessed. After the time-intensity curves (TIC) were drawn, the time to peak enhancement (TTP), peak intensity (PI) and the time from peak to one half (TFP) were calculated for the tumors and surrounding salivary parenchyma. Postoperatively, histopathologic examination of surgical specimens was used as the gold standard. Color Doppler ultrasonography showed no significant differences in PSV between tumors, significantly less adenolymphomas had Grade 0-1 vascularity compared to pleomorphic adenomas, and the RI was significantly lower in adenolymphomas compared to pleomorphic adenomas and malignant tumors. CEUS had acceptable diagnostic sensitivity, specificity, and accuracy for differential diagnosis of pleomorphic adenomas and adenolymphomas based on the diagnostic criteria of rim enhancement and slow wash-out rate, respectively. The sensitivity, specificity, and accuracy for differential diagnosis of malignant tumors based on the diagnostic criteria of an ill-defined enhancement margin, an enlarged enhancement area or a fast wash-in rate were also satisfactory. Accurate diagnosis of salivary gland tumors in clinical practice can be increased using color Doppler ultrasound and CEUS in combination with a case history and other imaging.

Evaluation of Renal Microperfusion in Diabetic Patients With Kidney Injury by Contrast-Enhanced Ultrasound.

To conduct a quantitative analysis of renal microvascular perfusion in diabetic patients with kidney injury using contrast-enhanced ultrasound (CEUS). A total of 172 patients with type 2 diabetes mellitus and kidney injury were recruited from May 2017 to November 2019. After collection of clinical characteristics, a CEUS examination was performed after injection of the contrast agent SonoVue (Bracco SpA, Milan, Italy). Time-intensity curves and renal perfusion parameters were analyzed. Ultrasound-guided renal biopsy was performed. The patients were divided into a diabetic nephropathy (DN) group and a nondiabetic renal disease (NDRD) group according to renal pathologic results. The discrimination of perfusion parameters between the groups was analyzed statistically with SPSS version 19.0 software (IBM Corporation, Armonk, NY). Receiver operating characteristic curves were used to illustrate the diagnostic performance of indicators. Ninety-eight patients, including 45 with DN (29 male; mean age ± SD, 57.76 ± 10.47 years) and 53 with NDRD (40 male; mean age, 48.7 ± 13.88 years) were included in this study. The peak enhancement (PE), wash-in the area under the curve (AUC), wash-in rate, wash-in perfusion index, wash-out AUC, wash-in and wash-out AUC, and wash-out rate were significantly different between the groups (P < .05). There were no differences in time-related parameters between the DN and NDRD groups (P > .05). The receiver operating characteristic curve analysis showed that the AUC for PE was 0.727, and PE lower than 7712.426 had diagnostic potential, with sensitivity of 81% and specificity of 40% in discriminating between NDRD and DN. The quantification of CEUS parameters can discriminate DN in diabetic patients with kidney injury. The PE and AUC may be feasible parameters.

Two-dimensional parametric parenchymal blood flow in transarterial chemoembolisation for hepatocellular carcinoma: perfusion change quantification and tumour response prediction at 3 months post-intervention

To evaluate the feasibility and potential value of two-dimensional (2D) parametric parenchymal blood flow (2D-PPBF) for the assessment of perfusion changes during transarterial chemoembolisation with drug-eluting beads (DEB-TACE) and to analyse correlations of 2D-PPBF parameters and tumour response. Thirty-two patients (six women, 26 men, mean age: 67±8.9 years) with unresectable hepatocellular carcinoma (HCC) who underwent their first DEB-TACE were included in this study. To quantify perfusion changes using 2D-PPBF, the acquired digital subtraction angiography (DSA) series were post-processed. Ratios were calculated between the reference region of interest (ROI) and the wash-in rate (WIR), the arrival to peak (AP) and the area under the curve (AUC) of the generated time-density curves. Comparisons between pre- and post-embolisation data were made using the Wilcoxon signed-rank test. Tumour response was assessed at 3 months using the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and correlated to changes of 2D-PPBF parameters. All 2D-PPBF parameters derived from the ROI-based time-attenuation curves were significantly different pre-versus post-DEB-TACE. Although the AUC, the WIR and target lesion size measured in accordance with mRECIST decreased (p≤0.0001) significantly, AP values showed a significant increase (p=0.0033). Tumour response after DEB-TACE correlated with changes in the AUC (p=0.01, r=-0.45). 2D-PPBF offers an objective approach to analyse perfusion changes of embolised tumour tissue following DEB-TACE and can therefore be used to predict tumour response.

Contrast-Enhanced Ultrasound Quantification Assessment of Focal Fatty Variations in Liver Parenchyma: Challenging the Traditional Qualitative Paradigm of Uniform Enhancement With Adjacent Parenchyma.

The purpose of this study was to quantify contrast-enhanced ultrasound enhancement of focal fatty sparing (FFS) and focal fatty infiltration (FFI) and compare it with adjacent liver parenchyma. This was a retrospective observational study yielding 42 cases in the last 4 years. Inclusion criteria were a focal liver lesion, adequate video availability, and an established diagnosis of FFS or FFI based on clinical or imaging follow-up or a second modality. Contrast-enhanced ultrasound examinations were performed with a standard low-mechanical index technique. Commercially available software calculated quantitative parameters for a focal liver lesion and a reference area of liver parenchyma, producing relative indices. In total, 42 patients were analyzed (19 male) with a median age of 18 (interquartile range, 42) years and a median lesion diameter of 30 (interquartile range, 16) mm. The cohort included 26 with FFS and 16 with FFI. Subjectively assessed, 27% of FFS and 25% of FFI were hypoenhancing in the arterial phase, and 73% of FFS and 75% of FFI were isoenhancing. In the venous and delayed phases, all lesions were isoenhancing. The peak enhancement (P = .001), wash-in area under the curve (P < .01), wash-in rate (P = .023), and wash-in perfusion index (P = .001) were significantly lower in FFS compared with adjacent parenchyma but not the mean transit time. In the FFI subgroup, no significant difference was detected. Comparing relative parameters, only the wash-in rate was significantly (P = .049) lower in FFS than FFI. The mean follow-up was 2.8 years. Focal fatty sparing shows significantly lower and slower enhancement than the liver parenchyma, whereas FFI enhances identically. Focal fatty sparing had a significantly slower enhancement than FFI.

Value of Diffusion-Weighted and Perfusion-Weighted MR Imaging in Differentiation of Recurrent Tongue Carcinoma from Post-Treatment Changes

Abstract Background: Tongue carcinoma is characterized by high recurrence rate. Thus, post-treatment follow-up imaging is critically important. Advanced Magnetic Resonance Imaging (MRI) techniques can be employed for this purpose due to the limited accuracy of conventional MRI. Aim of Study: Evaluation of the value of Diffusion Weight-ed (DW) and perfusion weighted MRI implementation in the post-treatment follow-up of tongue carcinoma. Patients and Methods: This study was conducted on 23 patients on post-treatment follow-up of tongue carcinoma. They underwent DW-MRI and Dynamic Contrast Enhanced (DCE) perfusion T1-weighted MRI to differentiate between recurrent tumor and post-treatment changes. Apparent Diffu-sion Coefficient (ADC) was estimated, perfusion MR quali-tative and semiquantitative assessment was performed. Re-sulting data were compared to histopathologic characterization (n=18) and further clinical and radiological follow-up (n=5) which were considered as the reference standards. Results: The mean ADC value of recurrent tongue carci-noma (1.029±0.207 X 10–3mm2/s) was significantly lower (p < 0.001) than the mean ADC value of post-treatment changes (1.425±0.238 X 10–3mm2/s). The ADC threshold used for differentiating recurrent tumor from post-treatment changes was 1.175 X 10–3mm2/s with Area Under the Curve (AUC) of 0.938 and diagnostic accuracy of 82.6%. Among the DCE perfusion weighted MR parameters, the wash in rate and Area Under Gadolinium Curve (AUGC) displayed the highest diagnostic accuracy (73.9%) with thresholds of 18.65a.u/s and 126826.7m.M.s respectively. The combined use of both DW-MRI and perfusion weighted MRI showed the highest diagnostic accuracy. Conclusion: The DW MRI is a non-invasive technique providing accurate post-treatment follow-up assessment of tongue carcinoma. The perfusion weighted MRI provides lower diagnostic accuracy than DWI. The combined use of both techniques provides superior differentiation of tumor recurrence from post-treatment changes.

Abstract 4263: Characterization of patient-specific drug delivery for breast cancer using image-guided computational fluid dynamics

Abstract Introduction: A tumor's blood supply and interstitial flow play an essential role in tumor growth, invasion, and treatment response. We have developed a methodology that employs quantitative MRI data to constrain a patient-specific, computational fluid dynamics (CFD) model of blood flow and interstitial transport within breast tumors. The dynamics of solute transport are characterized based on steady state flow fields, so that delivery of oxygen, nutrients, or therapies through the circulation can be estimated. It is a fundamentally new way to characterize breast tumor hemodynamics using MRI. Method: Eleven malignant and five benign lesions from 12 patients were included in this study. Vessel segmentation and tracking were performed to reconstruct the whole breast vasculature and to identify vessels feeding or draining tumors. Ultrafast dynamic contrast-enhanced MRI and diffusion-weighted imaging data were analyzed to estimate the bolus arrival time, Ktrans (volume transfer coefficient), and ADC (apparent diffusion coefficient); these data were used to spatially assign flow direction, local vascular permeability, and tissue density, respectively. The model of steady state flow was described by three components: 1) blood flow following Poiseuille's law, 2) interstitial flow following Darcy's law, and 3) flux transmitted across the vascular walls following Starling's law. The behavior of drug delivery was described by an advection-diffusion equation in the interstitial tissue, with the profile of the vascular bolus as a source term. The whole system was solved with a 1D-3D coupled implementation. At the end of analysis, the tracer's propagation through the tissue-of-interest was visualized and hemodynamic characteristics are derived to compare the malignant and benign lesions. Result: Visualization of the time-resolved distribution and propagation of solute demonstrated the intratumoral heterogeneity of accessibility to drugs. Furthermore, we are currently calculating the spatially-resolved accumulation, wash-in rate, and infiltration duration of different drugs for each lesion, so that a quantitative comparison can be performed between malignant and benign lesions. Conclusion: We have developed a computational model, informed by patient-specific MRI data, to simulate the blood supply, interstitial fluid environment, and intratumorally heterogeneous access to therapies for breast tumors. It represents the first methodology of integrating CFD with patient specific MRI data for quantifying the spatiotemporally resolved drug propagation as well as the entire pressure and flow fields within the breast. NCI U01CA142565, U01CA CA174706, and R01 CA218700. CPRIT RR160005. Citation Format: Chengyue Wu, David A. Hormuth, Federico Pineda, Gregory S. Karczmar, Robert D. Moser, Thomas E. Yankeelov. Characterization of patient-specific drug delivery for breast cancer using image-guided computational fluid dynamics [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4263.

Below-the-Ankle Arrival Time as a Novel Limb Tissue Perfusion Index: Two-dimensional Perfusion Angiography Evaluation

Purpose: To identify lower limb 2-dimensional (2D) perfusion angiographic parameters that are related to skin perfusion pressure (SPP), a predictor of wound healing in patients with chronic limb-threatening ischemia (CLTI) undergoing below-the-knee (BTK) endovascular treatment (EVT). Materials and Methods: Thirty-three consecutive patients (mean age 74.5 years; 18 men) with 47 isolated BTK lesions in 33 limbs (Rutherford category 3–5) underwent EVT. Dorsal and plantar SPPs were measured before EVT and the day after. The indexed blood flow below the ankle was measured using 2D perfusion angiography before and after EVT to determine changes in perfusion parameters [arrival time (AT), time to peak, wash-in rate, mean transit time, and width and area under the time-density curve] at rest vs during hyperemia induced with a 20-mg intra-arterial papaverine infusion. Correlations between the 2D perfusion parameters and SPPs were assessed using the Pearson coefficient. The cutoff points to predict mean SPPs >40 mm Hg were analyzed using a receiver operating characteristic curve; outcomes are reported as the area under the curve (AUC) with 95% confidence interval (CI). Results: After EVT at rest and during hyperemia, only AT was significantly changed, although hyperemia produced significant changes in all the pre-/post-EVT 2D perfusion parameters except the wash-in rate. Dorsal and plantar SPPs after EVT were significantly increased and correlated with hyperemic AT and the AT ratio (hyperemia/at rest values) below the ankle. Hyperemic ATs <6.3 seconds and AT ratios <0.78 were predictive factors for a mean SPP >40 mm Hg, with AUCs of 0.83 (95% CI 0.67 to 0.99) and 0.78 (95% CI 0.61 to 0.95), respectively. Conclusion: Hyperemic ATs <6.3 seconds or AT ratios <0.78 below the ankle may be essential to obtain sufficient SPPs for limb salvage in BTK lesions. Thus, the use of 2D perfusion angiography enabled the monitoring of lower limb tissue perfusion throughout EVT and may thereby optimize treatment of CLTI.

Game changers in vascular and endovascular surgery

Game changers in vascular and endovascular surgery

2D perfusion-angiography during endovascular intervention for critical limb threatening ischemia - A feasibility study.

PurposeTwo-dimensional perfusion angiography is a new method to quantify and evaluate tissue perfusion during endovascular intervention. The aim was to evaluate time-patterns and dynamics of contrast arrival and distribution before and after endovascular intervention in patients with critical limb threatening ischemia.MethodsData were collected from 37 patients with critical limb threatening ischemia due to infra-inguinal occlusive disease having a successful endovascular procedure. two-dimensional perfusion angiography was used as a post-processing software with analysis of numeric parameters related to arrival and distribution patterns of contrast.ResultsThirty-three patients were successfully analysed whereas four patients were excluded due to motion artefacts. All patients were successfully treated with recanalization of the superficial femoral, popliteal, below the knee-vessels or a combination. Short-term improvement at 30-day follow-up was noted both clinically and by ankle-brachial index and toe pressure measurements. A significant reduction in contrast arrival time between pre-and post-angioplasty runs was noted as measured by arrival time median 3.2 and interquartile range (2.5–4.2) vs. 2.6 (1.6–3.4) and time-to-peak 4.1 (3.6–5.0) vs. 3.1 (2.3–3.9) p = 0.009. An increased wash-in rate was also observed 18.3 (12.6–21) vs. 30.1 (22–30.5) p = 0.001 between pre-and post-angioplasty runs.ConclusionsThe use of perfusion angiography for evaluation of foot-circulation during endovascular interventions provides new information regarding quantitative assessment of contrast inflow before and after endovascular intervention without the need for extra contrast or runs. No selective catheterisation is necessary. The technique is easily adopted in a clinical setting. Further studies are necessary to create robust clinical endpoints.

Transcatheter intra-arterial perfusion (TRIP)-MRI biomarkers help detect immediate response to irreversible electroporation of rabbit VX2 liver tumor.

Irreversible electroporation (IRE) is a nonthermal tissue ablation technique that represents a promising treatment option for unresectable liver tumors, but the effectively treated zone cannot be reliably predicted. We investigate the potential benefit of transcatheter intra-arterial perfusion (TRIP) -MRI for the early noninvasive differentiation of IRE zone from surrounding reversibly electroporated (RE) zone. Seventeen rabbits with VX2 liver tumors were scanned with morphological and contrast-enhanced MRI sequences approximately 30 min after IRE tumor ablation. Quantitative TRIP-MRI perfusion parameters were evaluated in IRE zone and RE zone, defined according to histology. MRI and histology results were compared among zones using Wilcoxon rank-sum tests and correlations were evaluated by Pearson's correlation coefficient. There were significant differences in area under the curve, time to peak, maximum and late enhancement, wash-in and wash-out rates in the tumor IRE zones compared with the boundary tumor RE zones and untreated tumors. Histology showed significantly fewer tumor cells, microvessels and significantly more apoptosis in tumor IRE zones compared with tumor RE zones (-51%, -66% and +185%, respectively) and untreated tumors (-60%, -67%, and +228%, respectively). A strong correlation was observed between MRI and histology measurements of IRE zones (r = 0.948) and RE zones (r = 0.951). TRIP-MRI demonstrated the potential to detect immediate perfusion changes following IRE liver tumor ablation and effectively differentiate the IRE zone from the surrounding tumor RE zone.

P3395Arrival time at hyperemia of below the ankle as a determinant factor for limb salvage: evaluation by 2 dimension perfusion angiography

Abstract Background In patients with critical limb ischemia, it is desirable to obtain enough skin perfusion pressure (SPP) levels through revascularization. 2D-perfusion angiography is an emerging technology for the quantification of tissue perfusion consisted of 6 parameters calculated by time-density curve of digital subtraction angiography (DSA). Purpose We evaluated the feasibility of 2D-perfusion angiography for below the knee (BTK) endovascular therapy (EVT). We aimed to clarify which angiographical parameters of lower limb are related to SPP after EVT. Methods Consecutive 33 limbs (mean age 74.5 years, men 55%), which successfully underwent EVT for isolated BTK lesions, were enrolled in this study. We excluded Rutherford 6 limbs with severe gangrene or tissue loss, consequently 26 limbs were Rutherford 4 or 5 critical limb ischemia. We treated total 47 lesions, including 26 chronic total occlusive lesions. 5Fr guiding sheath was advanced to popliteal artery. DSA images were obtained by mechanical contrast infusion. We quantified indexed blood flow on below the ankle area by using 2D-perfusion angiography, and examined 6 parameters [arrival time (AT), time to peak (TTP), wash-in rate, width, area under the curve and mean transit time (MTT)] from acquired DSA. Hyperemia was induced by 20mg papaverine intra-arterial infusion through the guiding sheath. Results The parameters except wash-in rate were significantly shortened after hyperemia induced by intra-arterial papaverine infusion below the ankle region. Dorsal and plantar SPP were significantly correlated with hyperemic AT, hyperemic wash-in rate and AT ratio (hyperemic/rest) of lower ankle regions after EVT. However, only AT ratio was independently associated with dorsal SPP in multivariate analysis (P=0.032). A receiver operating characteristic curve showed hyperemic AT &lt;4.5 seconds and AT ratio &lt;0.49 predicted to obtain SPP levels &gt;50 mmHg after EVT with the area under the curve of 0.71 (95% confidence interval, 0.52–0.90) and 0.73 (95% confidence interval, 0.55–0.90), respectively. Representative Case of 2D-perfusion Conclusion Hyperemic AT &lt;4.5 seconds and AT ratio &lt;0.49 of lower ankle regions may be essential to obtain the sufficient levels of SPP for limb salvage after BTK intervention. 2D perfusion angiography technique at hyperemic condition is feasible and has the potential to monitor lower limb tissue perfusion through EVT and to optimize the interventional treatment.

Multiparametric MRI Evaluation of Complex Ovarian Masses

ObjectiveTo assess the role of diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging in the categorization of complex ovarian masses into benign and malignant. Materials and MethodsThis prospective study was done on 33 complex ovarian masses. T1 and T2-weighted sequences, diffusion-weighted imaging, apparent diffusion coefficient, and dynamic contrast-enhanced magnetic resonance imaging were performed on 1.5 T MRI. Time-intensity curves, tissue signal intensity on unenhanced T1 images (SI0), maximum absolute contrast enhancement (SImax), time to reach SImax (Tmax), maximum relative SI (SIrel = [SImax − SI0]/SI0 ×100), maximum Slope (Slopemax = SIrel/Tmax ×100), and wash in rate (WIR = [SImax − SI0]/Tmax) were calculated. Histopathological diagnosis was taken as gold standard. ResultsA total of 20/33 masses were benign, 2/33 were borderline tumors, and 11/33 were malignant. Diffusion restriction was seen in all malignant masses and 13/20 benign masses. The mean apparent diffusion coefficient values showed a significant difference between malignant and benign, with 81.8% sensitivity and 63.6% specificity. Type III curve showed 100% specificity for malignant lesions. Tmax and Slopemax were useful in differentiating benign and malignant masses; with Tmax cut-off at 73.5 seconds having a high specificity (81.8%) and Slopemax cut-off at 0.83%/s having high sensitivity (91%) and negative predictive value (94.4%). ConclusionMultiparametric MRI confers high diagnostic accuracy in stratifying complex ovarian masses.

Abstract 1942: Volume and vascular evolution assessed with ultrasound in tumor growth: First steps for a future tool of predictive responses of treatment

Abstract Background: Mathematical models have been developed to simulate tumor growth, as a goal to predict therapy response. We implemented three models and we investigated their agreement with tumor size assessed by ultrasound. We also investigated the link between microvascular flow parameters and future tumor size evolution. Methods: Three ordinary differential equation tumor growth models were implemented in Matlab. The exponential-linear model (EL) assumes growth rate tends to linear after initial exponential growth as nutrient support becomes limited. The Gompertz model (G) describes demographic growth with a fixed carrying capacity because growth cannot exceed the capacity of the environment. The dynamic carrying capacity model (DCC) assumes this carrying capacity can change with time, for example, due to angiogenesis or necrosis formation. Experimental data were acquired in 11 control and 10 antiangiogenic (AA) treated mice with ectopic murine colorectal carcinoma (CT26) on Days 7, 9, 13, 15 and 21 after implantation (therapy started at day 7). Ellipsoidal volume (V) was estimated from B-mode measurements of the major transverse and longitudinal axes and used to estimate Relative Growth Rate (RGR): (t{n}) = [V(t_{n}-V(t_{n-1})]/[(t_{n}-t_{n-1}).V(t_{n-1})]. Contrast-Enhanced Ultrasound (CEUS) data were acquired along the longitudinal axis with Sequoia 512, 7-14 MHz probe. Regions with no contrast-enhancement were identified. Average contrast intensity vs. time curves in the perfused zone were fit to a lognormal model to estimate Area Under the Curve (AUC), Peak Enhancement (PE), Time to Peak (TTP), Mean Transit Time (MTT), Wash In Rate (WIR) and Wash Out Rate (WOR). The Akaike Information Criterion (AIC) was used to evaluate the relative quality of the models to describe the tumor size evolution. AIC penalizes models with more parameters to deal with the trade-off between goodness of fit and the model’s simplicity. Results: Initial implementation of the models using a fixed (1 mm3) and free initial tumor size were compared. In this data set where earliest measured tumor size (day 4) varied from 15 to 39 mm3, the additional free parameter resulted in improved mean AIC (EL: 37 vs. 40 ; G: 37 vs. 41 ; DCC: 43 vs. 45 - free and fixed initial volume respectively). AIC was lowest on average for the G model in control mice. The TTP, WIR and WOR at t_n were linked with future RGR between t_n and t_{n+1} (RS = -0.51, 0.44 and -0.46 respectively for C (TTP and WIR) or AA (WOR) group, p&amp;lt;0.01, non-parametric Spearman correlation coefficient). Conclusions: The microvascular function includes additional information related to tumor growth. The integration of size and vascularization parameters into the mathematical models is the next step for predictive tumor growth. Such a model based on predictive quantitative ultrasound images has potential application in treatment follow-up. Citation Format: Jerome Griffon, Zixin Yang, Delphine Le Guillou-Buffello, Alexandre Dizeux, Michele Lamuraglia, Lori Bridal. Volume and vascular evolution assessed with ultrasound in tumor growth: First steps for a future tool of predictive responses of treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1942.

Abstract 4702: Characterization of ultrasound and immunohistochemichal parameters during development of murine tumor

Abstract Background: We compared the evolution of US index in vivo (morphological tumor size, tissue elasticity and microvascular flow) with whole-slice fluorescent immunohistochemical marker maps at different stages of murine tumor development. Methods: Murine colorectal carcinoma (CT26) was subcutaneously implanted in 49 mice on Day 0 (D0). Mice were randomized for data acquisition on D7, D10, D14, D16 and D17 (n = 10 each day except for D16 n = 9). Tumors were measured in B-mode along major transverse and longitudinal axes to estimate ellipsoidal volume. Contrast-Enhanced Ultrasound (CEUS) performed with Sequoia 512, 7-14 MHz probe and with syringe-pump-controlled bolus injection in the caudal vein of 40 μL of SonoVue (Bracco Suisse) and Shear-Wave Elastography (SWE; SSI, Aixplorer, SL 15-4 probe) maps were acquired along the longitudinal axis. Whole-slice histological sections were prepared with fluorescent immunohistochemical staining and parametric maps were made with in-house software to estimate the % area of nuclei, apoptosis (AP) and vascular endothelium (VE) marker. Regions with no contrast-enhancement were identified to estimate % perfused area (%P) and to construct perfused (P) and nonperfused (NP) masks that were then co-registered to SWE maps. Mean and standard deviation (SD) of the SWE could be calculated in whole tumor, P and NP zones. Average contrast intensity vs time curves in the P zone were fit to a lognormal model to estimate Area Under the Curve (AUC), Peak Enhancement (PE), Time to Peak (TTP), Mean Transit Time (MTT), Wash In Rate (WIR) and Wash Out Rate (WOR). The non-parametric Wilcoxon rank and Spearman tests were used to test respectively parameter evolution and correlation. Results: SWE and CEUS parameters did not correlate. SWE did not differ significantly for P and NP zones. Only TTP (RS = 0.47, p &amp;lt; 0.01) correlated positively with tumor volume. Overall, %P was high ( &amp;gt;= 75%) and did not correlate with tumor volume. Individual histological parameters did not change significantly with time or tumor volume, but % area of strong co-marking of VE and AP decreased significantly between D10 and D14/16. Conclusions: These preliminary results probe the relationship between tumor volume, functional-flow and elastic properties in tumors. One CEUS parameter correlated with tumor growth and thus appears to be sensitive to changes occurring during tumor development. Lack of correlation between SWE and CEUS parameters suggests that they provide complementary information. Nevertheless, it is better to understand the sensitivity of these non-invasive parameters to changes occurring during tumor development in order to obtain a predictive tumor growth parameter. The difference combination of these parameters will change the clinical practice, allowing an early therapeutic adaptation without loss of opportunity to take the good treatment for the patient and without unnecessary therapeutic costs. Citation Format: Jerome Griffon, Delphine Le Guillou-Buffello, Lori Bridal, Michele Lamuraglia. Characterization of ultrasound and immunohistochemichal parameters during development of murine tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4702.

Abstract 1946: Quantifying trastuzumab-induced alterations of intratumoral heterogeneity using MRI-derived tumor subregions in the preclinical setting

Abstract Introduction: Heterogeneity in the tumor microenvironment affects therapeutic delivery, providing a major challenge for cancer treatment. We investigate the ability of multi-parametric, voxel-based characterizations of tumor heterogeneity from quantitative magnetic resonance imaging (MRI) to spatially resolve physiological tumor subregions of response to anti-HER2 targeted therapy in a murine model of HER2+ breast cancer. Methods: BT474 cells were implanted in nude athymic mice (n=20) and tumors grown to ~225 mm3. Mice were randomly assigned to saline control or trastuzumab groups, with treatments given on days 0 and 3. Dynamic contrast enhanced (DCE) MRI and diffusion weighted (DW) MRI data were collected on days 0 (pre-treatment), 1 and 4. Tumors, excised on day 4, were processed for histology with anti-CD31 staining. Apparent diffusion coefficients (ADC, a measure of cell density) were extracted from DW-MRI data. DCE-MRI data was modeled to extract the extravascular, extracellular volume fraction, ve, and the volume transfer coefficients, Ktrans and kep, which correspond to the rate of wash-in and wash-out of contrast agent, respectively. Hierarchical clustering of tumor voxel data (ADC, ve, Ktrans, and kep) was used to identify physiological tumor subregions. The contribution of each subregion to tumor volume was quantified as percent tumor volume for each mouse and time point. Image analysis of histology data was used to generate vessel area and nuclei maps for whole-slice histology data. CD31 stained slices were subsequently divided into physiological subregions in terms of vessel and nuclei density, and the contribution of each subregion to the whole-slice area was quantified as percent tumor area. Results: Hierarchical clustering of the MRI data yielded four clusters: low vascularity - low cellularity (LV-LC), low vascularity - high cellularity (LV-HC), high vascularity - low cellularity (HV-LC), high vascularity - high cellularity (HV-HC). At day 0, no significant differences in cluster percent tumor volume were observed between control and treated tumors (p&amp;gt;0.05). At day 4, a significant decrease in LV-HC percent tumor volume was observed in treated tumors compared to control (mean 13.7% vs. 35.0%, p=0.04). Histology subregion analysis corroborated in vivo imaging findings, with treated tumors having significantly lower LV-HC percent tumor area compared to control (mean 26.8% vs 53.6%, p&amp;lt;0.01). Conclusion: High-dimensional analysis of quantitative MRI parameter maps can be utilized to identify physiological subregions of tumor response, and can be biologically validated using histology data. The results suggest trastuzumab therapy decreases the hypoxic (LV-HC) tumor volume. Quantifying tumor microenvironment alterations in response to therapy can potentially be used to predict response for patients with HER2+ breast cancer. Citation Format: Anum Syed, Jennifer Whisenant, Anna Sorace, Thomas Yankeelov. Quantifying trastuzumab-induced alterations of intratumoral heterogeneity using MRI-derived tumor subregions in the preclinical setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1946.

Dynamic contrast-enhanced magnetic resonance imaging perfusion characteristics in meningiomas treated with resection and adjuvant radiosurgery.

OBJECTIVEThere is a need for advanced imaging biomarkers to improve radiation treatment planning and response assessment. T1-weighted dynamic contrast-enhanced perfusion MRI (DCE MRI) allows quantitative assessment of tissue perfusion and blood-brain barrier dysfunction and has entered clinical practice in the management of primary and secondary brain neoplasms. The authors sought to retrospectively investigate DCE MRI parameters in meningiomas treated with resection and adjuvant radiation therapy using volumetric segmentation.METHODSA retrospective review of more than 300 patients with meningiomas resected between January 2015 and December 2018 identified 14 eligible patients with 18 meningiomas who underwent resection and adjuvant radiotherapy. Patients were excluded if they did not undergo adjuvant radiation therapy or DCE MRI. Demographic and clinical characteristics were obtained and compared to DCE perfusion metrics, including mean plasma volume (vp), extracellular volume (ve), volume transfer constant (Ktrans), rate constant (kep), and wash-in rate of contrast into the tissue, which were derived from volumetric analysis of the enhancing volumes of interest.RESULTSThe mean patient age was 64 years (range 49-86 years), and 50% of patients (7/14) were female. The average tumor volume was 8.07 cm3 (range 0.21-27.89 cm3). The median Ki-67 in the cohort was 15%. When stratified by median Ki-67, patients with Ki-67 greater than 15% had lower median vp (0.02 vs 0.10, p = 0.002), and lower median wash-in rate (1.27 vs 4.08 sec-1, p = 0.04) than patients with Ki-67 of 15% or below. Logistic regression analysis demonstrated a statistically significant, moderate positive correlation between ve and time to progression (r = 0.49, p < 0.05). Furthermore, there was a moderate positive correlation between Ktrans and time to progression, which approached, but did not reach, statistical significance (r = 0.48, p = 0.05).CONCLUSIONSThis study demonstrates a potential role for DCE MRI in the preoperative characterization and stratification of meningiomas, laying the foundation for future prospective studies incorporating DCE as a biomarker in meningioma diagnosis and treatment planning.