Intraarterial contrast-enhanced ultrasound to predict the short-term tumour response of hepatocellular carcinoma to Transarterial chemoembolization with Lipiodol.

BACKGROUND: Transarterial chemoembolization (TACE) is an effective locoregional therapy in hepatocellular carcinoma (HCC). However, it is difficult to predict the tumour response (TR) of TACE intraprocedurally. The aim of this study was to predict the TR after TACE (1-3 months) in HCC patients using intraprocedural intraarterial contrast enhanced ultrasound (IA-CEUS). METHODS: In this case-control study, consecutive patients who received TACE in our hospital from September 2018 to May 2019 were enrolled. IA-CEUS was performed before and after TACE. Postoperative contrast-enhanced liver MRI was performed 1-3 months after TACE as the gold standard. According to the modified Response Evaluation Criteria in Solid Tumours (mRECIST), ultrasonic manifestations were compared between the complete remission (CR) group and non-CR group by univariate and multivariate analyses. A logistic predictive model was established and validated, and its diagnostic efficiency was evaluated. RESULTS: Forty-four patients with sixty-one lesions were enrolled in the study. Multivariate analysis identified, the risk factors as a large lesion diameter (OR: 1.84; 95% confidence interval [CI]: 1.009, 3.080; P = 0.020), a larger dimension of non-enhancing area in superior mesenteric artery (SMA)-CEUS than the size in B-mode ultrasound preoperatively (OR: 3.379; 95% CI: 1.346,8.484; P = 0.010), presence of corona enhancement in hepatic artery (HA)-CEUS postoperatively (OR: 6.642; 95% CI: 1.214, 36.331; P = 0.029), and decreased corona enhancement thickness (per centimetre) postoperatively (OR: 0.025; 95% CI: 0.006,0.718; P = 0.025). The area under the receiver operating characteristic curve (AUROC) of the predictive model was 0.904 (95% CI: 0.804, 0.966; P < 0.001). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 81.08, 91.67, 85.25, 93.75, and 75.86%, respectively. Leave-one-out cross-validation (LOOCV) showed that the accuracy was 77.05%. CONCLUSIONS: Intraprocedural IA-CEUS can be used to predict the TR in HCC patients after TACE.

Anti-HER2 VHH Targeted Fluorescent Liposome as Bimodal Nanoparticle for Drug Delivery and Optical Imaging.

OBJECTIVES: The aim of this study was to formulate fluorescent-labeled targeted immunoliposome to visualize the delivery and distribution of drugs in real-time. METHODS: In this study, fluorescent-labeled liposomes were decorated with anti-HER2 VHH or Herceptin to improve the monitoring of intracellular drug delivery and tumor cell tracking with minimal side effects. The conjugation efficiency of antibodies was analyzed by SDS-PAGE silver staining. In addition, the physicochemical characterization of liposomes was performed using DLS and TEM. Finally, confocal microscopy visualized nanoparticles in the target cells. RESULTS: Quantitative and qualitative methods characterized the intracellular uptake of 110±10 nm particles with near 70% conjugation efficiency. In addition, live-cell trafficking during hours of incubation was monitored by wide-field microscopy imaging. The results show that the fluorescent- labeled nanoparticles can specifically bind to HER2-positive breast cancer with minimal off-target delivery. CONCLUSION: These nanoparticles can have several applications in personalized medicine, especially drug delivery and real-time visualization of cancer therapy. Moreover, this method also can be applied in the targeted delivery of contrast agents in imaging and thermotherapy.

The correlation with tumor radiological characteristics and prognosis of patients with early-stage hepatocellular carcinoma receiving transcatheter arterial chemoembolization.

ABSTRACT: Transcatheter arterial chemoembolization (TACE) is a standard treatment modality for intermediate stage hepatocellular carcinoma (HCC). The aim of this study was to determine the tumor radiological characteristics associated with prognosis of patients with early-staged HCC receiving TACE.Patients with BCLC stage A HCC were enrolled at Taichung Veterans General Hospital from January 2005 to December 2009. According to mRECIST criteria, patients with or without complete response (CR) were assigned to either the CR group or the non-CR group. Clinical and radiological characteristics were compared between the two groups.In 40 enrolled patients, 24 (60%) were in the CR group, and 16 (40%) in the non-CR group. Clinical parameters were similar between the 2 groups. Radiological characteristics including complete lipidol retention and the absence of residual tumor blush were significantly correlated with achievement of CR in the patients with small-sized HCC. Patients with CR after TACE had a significantly longer overall survival than those without (31.29 vs 22.63 months, P = .021).Complete lipidol retention and the absence of residual tumor blush were correlated with the radiological complete tumor response of these patients with small-sized early-stage HCC receiving TACE.

Acute Kidney Injury After CT in Emergency Patients with Chronic Kidney Disease: A Propensity Score-matched Analysis.

INTRODUCTION: Acute kidney injury (AKI) after intravenous contrast administration for computed tomography (CT) occurs infrequently, but certain patients may be susceptible. This study evaluated AKI incidence among emergency department (ED) patients with pre-existing chronic kidney disease (CKD) undergoing CT exams. METHODS: This retrospective cohort study in an integrated healthcare system included ED patients previously diagnosed with CKD stages 3-5 (estimated glomerular filtration rate <60 milliliters per minute per 1.73 meters squared over at least three months), undergoing CT exams with or without intravenous contrast, from January 1, 2013-December 31, 2017. We excluded patients with CT prior to (30 days) or following (14 days) index CT and missing serum creatinine (sCr) measurements. We applied propensity score matching, and then multivariable regression adjustment for post-CT ED disposition and ED diagnosis, to calculate adjusted risk of AKI. Secondary patient-centered outcomes included 30-day mortality, end-stage renal disease (ESRD) diagnosis, and dialysis initiation. RESULTS: Among 103,573 eligible ED patients undergoing CT, propensity score matching yielded 5,589 pairs. Adjusted risk ratio (ARR) for AKI was higher overall for contrast-enhanced CT (1.60; 95% confidence interval [CI], 1.43-1.79). However, secondary outcomes were infrequent: 19/5,589 non-contrast vs 40/5,589 contrast patients with new dialysis initiation at 30 days (adjusted risk 0.3% vs 0.7%; adjusted risk reduction 0.4%; 95% CI, 0.1%-0.7%). CONCLUSION: In ED patients with chronic kidney disease undergoing CT, intravenous contrast was associated with higher overall adjusted risk of AKI, but patient-centered secondary outcomes were rare. The clinical significance of transient kidney injury after CT is unclear, although patients with advanced chronic kidney disease appear to have elevated risk.

Optimized Bolus Threshold for Dual-Energy CT Angiography with Monoenergetic Images: A Randomized Clinical Trial.

Background The bolus-tracking technique from single-energy CT has been applied to dual-energy CT (DECT) without optimization or validation. Further optimization is imperative because of a paucity of literature and differences in the attenuation profile of virtual monoenergetic images (VMIs). Purpose To determine the optimal trigger threshold with bolus-tracking technique for DECT angiography (DECTA) in a phantom study and assess the feasibility of an optimized threshold for bolus-tracking technique in DECTA at 40 keV with a 50% reduced iodine dose in human participants. Materials and Methods A phantom study with rapid kilovoltage-switching DECT was performed to determine the optimal threshold for each kiloelectron-volt VMI. In a prospective study, consecutive participants who underwent whole-body CT angiography (CTA) from August 2018 to July 2019 were randomized into three groups: single-energy CTA (SECTA) with standard iodine dose (600 mg of iodine per kilogram), DECTA with 50% reduced iodine dose (300 mg of iodine per kilogram) by using a conventional threshold, and DECTA with 300 mg of iodine per kilogram by using an optimized threshold. A trigger threshold of 100 HU at 120 kVp was used as a reference for comparison. Injected iodine doses and aortic CT numbers were compared among the three groups using Kruskal-Wallis test. Results Ninety-six participants (mean age ± standard deviation, 72 years ± 9; 80 men) were evaluated (32 participants in each group). The optimized threshold for VMIs at 40 keV was 30 HU. The median iodine dose was lower in the optimized DECTA group (13 g) compared with conventional DECTA (19 g) and SECTA (26 g) groups (P < .017 for each comparison). The median aortic CT numbers were higher in the order corresponding to conventional DECTA (655-769 HU), optimized DECTA (543-610 HU), and SECTA (343-359 HU) groups (P < .001). Conclusion The optimized trigger threshold of 30 HU for bolus-tracking technique during dual-energy CT angiography at 40 keV achieved lower iodine load while maintaining aortic enhancement. ©RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Malayeri in this issue.

Spinal Syrinx Due to Lipiodol-Induced Arachnoiditis.

We present a case of a progressive symptomatic intramedullary cyst, diagnosed decades after Lipiodol injection. Lipiodol was originally administered intrathecally for the radiologic diagnosis of spinal masses. A link between the lesion and the history of Lipiodol injection was never suspected. Surgical exploration revealed a membrane above the lesion, separating the intradural space in a cranial and caudal compartment. On the level of the cyst, we identified glassy pearls containing a fatty liquid, compatible with Lipiodol deposits. We hypothesize that the syrinx is secondary to the impact of cerebrospinal fluid pulsations on the reactive membrane and that this membrane originated from an arachnoiditis caused by Lipiodol deposits. Lipiodol was indeed abandoned after it was found to cause arachnoiditis and neurologic sequelae. Despite the cessation of its usage, the causal role of Lipiodol in arachnoiditis and spinal cyst formation should still be considered, as symptoms may arise many years after Lipiodol administration.

Standardization of conventional chemoembolization for hepatocellular carcinoma.

INTRODUCTION AND OBJECTIVES: Conventional transarterial chemoembolization (cTACE) has several limitations due to the lack of standardization. The aim of this study was to evaluate the chemical and physical characteristics and behaviors over time of emulsions for cTACE and to assess intra- and inter-operator variabilities in the preparation processes. MATERIALS AND METHODS: This in vitro study involved evaluation of emulsions for cTACE prepared using two methods: water-in-oil (WiO) and chemotherapeutic-in-oil (CiO). Three emulsions were prepared with each method and obtained after 20, 50, and 100 pumping exchanges. A drop from each final mixture was analyzed via light microscopy (time 1) and after 5, 10, 15, and 20min since the end of preparation. After 20min, all preparations were re-mixed and new drops were re-evaluated. The intra- and inter-operator variabilities were analyzed. RESULTS: The mean droplet diameter decreased non-significantly when the number of pumping exchanges increased and increased significantly over time for both WiO and CiO. The droplets returned to their initial diameters after re-mixing. There were no significant differences in the intra- and inter-operator variabilities (P>0.01). CONCLUSIONS: Any interventional radiologist, regardless of their experience, may prepare these emulsions. These data may represent a set of instructions to standardize cTACE.

Combination therapy by transarterial injection of miriplatin-iodized oil suspension with radiofrequency ablation (RFA) versus microwave ablation (MWA) for small hepatocellular carcinoma: a comparison of therapeutic efficacy.

PURPOSE: To compare the technical efficacy and complications of the transarterial injection of a miriplatin-iodized oil suspension combined with radiofrequency ablation (RFA) or microwave ablation (MWA) in the treatment of small hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: This retrospective study included 123 HCCs in 101 patients treated with the transarterial injection of a miriplatin-iodized oil suspension and RFA (MPT-RFA) (maximum diameter: 1.5 [Formula: see text] 0.5 cm, range: 0.6-3.0 cm) and 68 HCCs in 49 patients treated with the transarterial injection of a miriplatin-iodized oil suspension and MWA (MPT-MWA) (maximum diameter: 1.6 [Formula: see text] 0.7 cm, range: 0.5-3.0 cm). Technical success was defined as the achievement of an ablative margin of at least 5 mm for each tumor. Technical success, complications, and local tumor progression were compared between the two groups. RESULTS: The initial technical success rate was significantly higher with MPT-MWA (94.1%) than with MPT-RFA (76.4%; P = 0.003). The number of treatment sessions per nodule was significantly lower with MPT-MWA (1.1) than with MPT-RFA (1.3) (P = 0.004). The major complication rates were similar with MPT-RFA (5.8%) and MPT-MWA (2.7%) (P = 0.391). The one-year local tumor progression rate was similar between MPT-RFA (0%) and MPT-MWA (0%) (P = 0.73). CONCLUSION: MPT-MWA may have improved therapeutic efficiency in the treatment of small HCCs.

Spectral CT-Based Iodized Oil Quantification to Predict Tumor Response Following Chemoembolization of Hepatocellular Carcinoma.

PURPOSE: To quantify iodized oil retention in tumors after transarterial chemoembolization using spectral computed tomography (CT) imaging in patients with hepatocellular carcinoma (HCC) and evaluate its performance in predicting 12-month tumor responses. MATERIALS AND METHODS: From September 2017 to December 2018, 111 patients with HCC underwent initial conventional transarterial chemoembolization. Immediately after the procedure, unenhanced CT was performed using a spectral CT scanner, and the iodized oil densities in index tumors were measured. In tumor-level analyses, a threshold level of iodized oil density in the tumors was calculated using clustered receiver operating characteristic curve analyses to predict the 12-month tumor responses. In patient-level analyses, significant factors associated with a 12-month complete response, including the presence of tumors below the threshold value (ie, suspected residual tumors), were evaluated by logistic regression. RESULTS: Forty-eight HCCs in 39 patients were included in the analyses. The lower 10th percentile of the iodine density was identified as the threshold for determining the 12-month nonviable responses. The area under the curve of the iodine density measurements in predicting the 12-month nonviable responses was 0.893 (95% confidence interval, 0.797-0.989). The threshold value of the iodine density of 10.68 mg/mL yielded a sensitivity of 82.76% and specificity of 94.74% (P < .001). In the patient-level analysis, the 12-month complete response was significantly associated with the presence of a suspected residual tumor, with an odds ratio of 72.0 (95% confidence interval, 7.273-712.770). CONCLUSIONS: Spectral CT imaging using quantitative analysis of the iodized oil retention in target HCCs can predict tumor responses after a conventional transarterial chemoembolization procedure.

Feasibility and Safety of n-Butyl Cyanoacrylate-Lipiodol-Iopamidol as an Alternative Liquid Embolic Material.

PURPOSE: To evaluate the feasibility and safety of n-butyl cyanoacrylate (NBCA)-Lipiodol-Iopamidol (NLI) as a liquid embolic material. MATERIALS AND METHODS: In vitro, the ratio of NLI components was adjusted and the configuration of the mixtures was assessed visually in saline. In vivo, 14 wide-necked aneurysms were created on the common carotid and external iliac arteries of four female swine. Under balloon occlusion, 12 aneurysms were embolized with NLI prepared at a NBCA-Lipidol-Iopamidol ratio of 2:3:1 (NLI231), and two were embolized with NBCA-Lipiodol (NL) prepared at a NBCA-Lipiodol ratio of 1:2 (NL12) as a trial group. We performed angiography to evaluate the effectiveness of embolization and adhesion of the embolic material to the balloons or microcatheters. RESULTS: In vitro, NLI231 (33% NBCA) was considered to be the optimal ratio for aneurysm embolization based on its configuration and stability. In vivo, embolization using NLI231 was successful and no adhesion between the embolic material and the balloons or microcatheters was observed in all 12 aneurysms. Embolization with NL12 was impossible in the other two aneurysms due to leakage and adhesion of NL. CONCLUSION: The configuration of NLI changed at each ratio. NLI231 is a feasible and safe liquid embolic material for balloon-assisted embolization of wide-necked aneurysms in swine.

Evaluation of Pelvic Anastomosis by Endoscopic and Contrast Studies Prior to Ileostomy Closure: Are Both Necessary? A Single Institution Review.

Contrast enema is the gold standard technique for evaluating a pelvic anastomosis (PA) prior to ileostomy closure. With the increasing use of flexible endoscopic modalities, the need for contrast studies may be unnecessary. The objective of this study is to compare flexible endoscopy and contrast studies for anastomotic inspection prior to defunctioning stoma reversal. Patients with a protected PA undergoing ileostomy closure between July 2014 and June 2019 at our institution were retrospectively identified. Demographics and clinical outcomes in patients undergoing preoperative evaluation with endoscopic and/or contrast studies were analyzed. We identified 207 patients undergoing ileostomy closure. According to surgeon's preference, 91 patients underwent only flexible endoscopy (FE) and 100 patients underwent both endoscopic and contrast evaluation (FE + CE) prior to reversal. There was no significant difference in pelvic anastomotic leak (2.2% vs. 1%), anastomotic stricture (1.1% vs. 6%), pelvic abscess (2.2% vs. 3.0%), or postoperative anastomotic complications (4.4% vs. 9%) between groups FE and FE + CE (P > .05). Flexible endoscopy alone appears to be an acceptable technique for anastomotic evaluation prior to ileostomy closure. Further studies are needed to determine the effectiveness of different diagnostic modalities for pelvic anastomotic inspection.

Association of breast cancer with MRI background parenchymal enhancement: the IMAGINE case-control study.

BACKGROUND: Background parenchymal enhancement (BPE) on breast magnetic resonance imaging (MRI) may be associated with breast cancer risk, but previous studies of the association are equivocal and limited by incomplete blinding of BPE assessment. In this study, we evaluated the association between BPE and breast cancer based on fully blinded assessments of BPE in the unaffected breast. METHODS: The Imaging and Epidemiology (IMAGINE) study is a multicenter breast cancer case-control study of women receiving diagnostic, screening, or follow-up breast MRI, recruited from three comprehensive cancer centers in the USA. Cases had a first diagnosis of unilateral breast cancer and controls had no history of or current breast cancer. A single board-certified breast radiologist with 12 years' experience, blinded to case-control status and clinical information, assessed the unaffected breast for BPE without view of the affected breast of cases (or the corresponding breast laterality of controls). The association between BPE and breast cancer was estimated by multivariable logistic regression separately for premenopausal and postmenopausal women. RESULTS: The analytic dataset included 835 cases and 963 controls. Adjusting for fibroglandular tissue (breast density), age, race/ethnicity, BMI, parity, family history of breast cancer, BRCA1/BRCA2 mutations, and other confounders, moderate/marked BPE (vs minimal/mild BPE) was associated with breast cancer among premenopausal women [odds ratio (OR) 1.49, 95% CI 1.05-2.11; p = 0.02]. Among postmenopausal women, mild/moderate/marked vs minimal BPE had a similar, but statistically non-significant, association with breast cancer (OR 1.45, 95% CI 0.92-2.27; p = 0.1). CONCLUSIONS: BPE is associated with breast cancer in premenopausal women, and possibly postmenopausal women, after adjustment for breast density and confounders. Our results suggest that BPE should be evaluated alongside breast density for inclusion in models predicting breast cancer risk.

Palladium-based nanomaterials for cancer imaging and therapy.

In recent decade, palladium-based (Pd-based) nanomaterials have shown significant potential for biomedical applications because of their unique optical properties, excellent biocompatibility and high stability in physiological environment. Compared with other intensively studied noble nanomaterials, such as gold (Au) and silver (Ag) nanomaterials, research on Pd-based nanomaterials started late, but the distinctive features, such as high photothermal conversion efficiency and high photothermal stability, have made them getting great attention in the field of nanomedicine. The goal of this review is to provide a comprehensive and critical perspective on the recent progress of Pd-based nanomaterials as imaging contrast agents and therapeutic agents. The imaging section focuses on applications in photoacoustic (PA) imaging, single-photon emission computed tomography (SPECT) imaging, computed tomography (CT) imaging and magnetic resonance (MR) imaging. For treatment of cancer, single photothermal therapy (PTT) and PTT combined with other therapeutic modalities will be discussed. Finally, the safety concerns, forthcoming challenges and perspective of Pd-based nanomaterials on biomedical applications will be presented.

Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice.

MRI sensitivity for diagnosis and localization of early myocarditis is limited, although it is of central clinical interest. The aim of this project was to test a contrast agent targeting activated platelets consisting of microparticles of iron oxide (MPIO) conjugated to a single-chain antibody directed against ligand-induced binding sites (LIBS) of activated glycoprotein IIb/IIIa (= LIBS-MPIO). Myocarditis was induced by subcutaneous injection of an emulsion of porcine cardiac myosin and complete Freund's adjuvant in mice. 3D 7 T in-vivo MRI showed focal signal effects in LIBS-MPIO injected mice 2 days after induction of myocarditis, whereas in control-MPIO injected mice no signal was detectable. Histology confirmed CD41-positive staining, indicating platelet involvement in myocarditis in mice as well as in human specimens with significantly higher LIBS-MPIO binding compared to control-MPIO in both species. Quantification of the myocardial MRI signal confirmed a signal decrease after LIBS-MPIO injection and significant less signal in comparison to control-MPIO injection. These data show, that platelets are involved in inflammation during the course of myocarditis in mice and humans. They can be imaged non-invasively with LIBS-MPIO by molecular MRI at an early time point of the inflammation in mice, which is a valuable approach for preclinical models and of interest for both diagnostic and prognostic purposes.

Sodium Cholate Bile Acid-Stabilized Ferumoxytol-Doxorubicin-Lipiodol Emulsion for Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma.

PURPOSE: To develop bile acid-stabilized multimodal magnetic resonance (MR) imaging and computed tomography (CT)-visible doxorubicin eluting lipiodol emulsion for transarterial chemoembolization of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Ferumoxytol, a US Food and Drug Administration-approved iron oxide nanoparticle visible under MR imaging was electrostatically complexed with doxorubicin (DOX). An amphiphilic bile acid, sodium cholate (SC), was used to form a stable dispersion of ferumoxytol-DOX complex in lipiodol emulsion. Properties of the fabricated emulsion were characterized in various component ratios. Release kinetics of DOX were evaluated for the chemoembolization applications. Finally, in vivo multimodal MR imaging/CT imaging properties and potential therapeutic effects upon intra-arterial (IA) infusion bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion were evaluated in orthotopic McA-Rh7777 HCC rat models. RESULTS: DOX complexed with ferumoxytol through electrostatic interaction. Amphiphilic SC bile acid at the interface between the aqueous ferumoxytol-DOX complexes and lipiodol enabled a sustained DOX release (17.2 ± 1.6% at 24 hours) at an optimized component ratio. In McA Rh7777 rat HCC model, IA-infused emulsion showed a significant contrast around tumor in both T2-weighted MR imaging and CT images (P = .044). Hematoxylin and eosin and Prussian blue staining confirmed the local deposition of IA-infused SC bile acid-stabilized emulsion in the tumor. The deposited emulsion induced significant increases in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) stain-positive cancer cell apoptosis compared to those in a group treated with the nonstabilized emulsion. CONCLUSIONS: SC bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion demonstrated sustained drug release and multimodal MR imaging/CT imaging capabilities. The new lipiodol-based formulation may enhance the therapeutic efficacy of chemoembolization in HCC.

Diagnostic Yield of Electroanatomic Voltage Mapping in Guiding Endomyocardial Biopsies.

BACKGROUND: Electroanatomic voltage mapping (EVM) is a promising modality for guiding endomyocardial biopsies (EMBs). However, few data support its feasibility and safety. We now report the largest cohort of patients undergoing EVM-guided EMBs to show its diagnostic yield and to compare it with a cardiac magnetic resonance (CMR)-guided approach. METHODS: We included 162 consecutive patients undergoing EMB at our institution from 2010 to 2019. EMB was performed in pathological areas identified at EVM and CMR. CMR and EVM sensitivity and specificity regarding the identification of pathological substrates of myocardium were evaluated according to EMB results. RESULTS: Preoperative CMR showed late gadolinium enhancement in 70% of the patients, whereas EVM identified areas of low voltage in 61%. Right (73%), left (19%), or both ventricles (8%) underwent sampling. EVM proved to have sensitivity similar to CMR (74% versus 77%), with specificity being 70% and 47%, respectively. In 12 patients with EMB-proven cardiomyopathy, EVM identified pathological areas that had been undetected at CMR evaluation. Sensitivity of pooled EVM and CMR was as high as 95%. EMB analysis allowed us to reach a new diagnosis, different from the suspected clinical diagnosis, in 39% of patients. The complications rate was low, mostly related to vascular access, with no patients requiring urgent management. CONCLUSIONS: EVM proved to be a promising tool for targeted EMB because of its sensitivity and specificity for identification of myocardial pathological substrates. EVM was demonstrated to have accuracy similar to CMR. EVM and CMR together conferred a positive predictive value of 89% on EMB.

Molecular MRI of the Immuno-Metabolic Interplay in a Rabbit Liver Tumor Model: A Biomarker for Resistance Mechanisms in Tumor-targeted Therapy?

Background The immuno-metabolic interplay has gained interest for determining and targeting immunosuppressive tumor micro-environments that remain a barrier to current immuno-oncologic therapies in hepatocellular carcinoma. Purpose To develop molecular MRI tools to reveal resistance mechanisms to immuno-oncologic therapies caused by the immuno-metabolic interplay in a translational liver cancer model. Materials and Methods A total of 21 VX2 liver tumor-bearing New Zealand white rabbits were used between October 2018 and February 2020. Rabbits were divided into three groups. Group A (n = 3) underwent intra-arterial infusion of gadolinium 160 (160Gd)-labeled anti-human leukocyte antigen-DR isotope (HLA-DR) antibodies to detect antigen-presenting immune cells. Group B (n = 3) received rhodamine-conjugated superparamagnetic iron oxide nanoparticles (SPIONs) intravenously to detect macrophages. These six rabbits underwent 3-T MRI, including T1- and T2-weighted imaging, before and 24 hours after contrast material administration. Group C (n = 15) underwent extracellular pH mapping with use of MR spectroscopy. Of those 15 rabbits, six underwent conventional transarterial chemoembolization (TACE), four underwent conventional TACE with extracellular pH-buffering bicarbonate, and five served as untreated controls. MRI signal intensity distribution was validated by using immunohistochemistry staining of HLA-DR and CD11b, Prussian blue iron staining, fluorescence microscopy of rhodamine, and imaging mass cytometry (IMC) of gadolinium. Statistical analysis included Mann-Whitney U and Kruskal-Wallis tests. Results T1-weighted MRI with 160Gd-labeled antibodies revealed localized peritumoral ring enhancement, which corresponded to gadolinium distribution detected with IMC. T2-weighted MRI with SPIONs showed curvilinear signal intensity representing selective peritumoral deposition in macrophages. Extracellular pH-specific MR spectroscopy of untreated liver tumors showed acidosis (mean extracellular pH, 6.78 ± 0.09) compared with liver parenchyma (mean extracellular pH, 7.18 ± 0.03) (P = .008) and peritumoral immune cell exclusion. Normalization of tumor extracellular pH (mean, 6.96 ± 0.05; P = .02) using bicarbonate during TACE increased peri- and intratumoral immune cell infiltration (P = .002). Conclusion MRI in a rabbit liver tumor model was used to visualize resistance mechanisms mediated by the immuno-metabolic interplay that inform susceptibility and response to immuno-oncologic therapies, providing a therapeutic strategy to restore immune permissiveness in liver cancer. © RSNA, 2020 Online supplemental material is available for this article.

MR enterocolonography in patients with Crohn's disease and healthy volunteers - Do we achieve diagnostic bowel distension?

PURPOSE: The aim of our prospective randomized study was to assess diagnostic quality and stability of bowel distension in patients with Crohn's disease (CD) and healthy volunteers subjected to synchronous magnetic resonance enterography and colonography (MREC), as well as to test the role of water enema and intravenous spasmolytics. The influence of gastric content, age, gender, and body mass on bowel distension was also evaluated. METHOD: Study groups included 164 CD patients and 53 healthy volunteers. After bowel preparation, randomized subgroups started ingestion ≥1000 mL of hyperosmolar solution within 30, 45, 60, 75, and 90 min before admission to MRI, respectively. Patients were examined in prone position and water enema was applied. Spasmolytics were administered prior to I.V. gadolinium. Distension of five bowel segments was independently assessed by two experienced radiologists. RESULTS: MREC yields diagnostic distension of the jejunum in 81.1 % and 79.2 % patients in the CD group and controls, respectively. For the terminal ileum it was >94 % in both groups. Good and excellent distension was achieved in other bowel segments. Distension was maintained up to 75 min from the start of oral ingestion. Water enema and spasmolytics significantly and independently improved distension of the small bowel. Distension of the cecum after spasmolytics was decreased. Gastric content, age, gender and body mass had no significant influence of bowel distension. CONCLUSIONS: MREC enables diagnostic distension of the colon and ileum (including terminal segment) in CD patients and healthy volunteers and diagnostically acceptable distension of the jejunum.

Impact of breath-hold level on positional error aligned by stent/Lipiodol in Hepatobiliary radiotherapy with breath-hold respiratory control.

BACKGROUND: Respiratory motion management with breath hold for patients with hepatobiliary cancers remain a challenge in the precise positioning for radiotherapy. We compared different image-guided alignment markers for estimating positional errors, and investigated the factors associated with positional errors under breath-hold control. METHODS: Spirometric motion management system (SDX) for breath holds was used in 44 patients with hepatobiliary tumor. Among them, 28 patients had a stent or embolized materials (lipiodol) as alignment markers. Cone-beam computed tomography (CBCT) and kV-orthogonal images were compared for accuracy between different alignment references. Breath-hold level (BHL) was practiced, and BHL variation (ΔBHL) was defined as the standard deviation in differences between actual BHLs and baseline BHL. Mean BHL, ΔBHL, and body-related factors were analyzed for the association with positional errors. RESULTS: Using the reference CBCT, the correlations of positional errors were significantly higher in those with stent/lipiodol than when the vertebral bone was used for alignment in three dimensions. Patients with mean BHL > 1.4 L were significantly taller (167.6 cm vs. 161.6 cm, p = 0.03) and heavier (67.1 kg vs. 57.4 kg, p = 0.02), and had different positional error in the craniocaudal direction (- 0.26 cm [caudally] vs. + 0.09 cm [cranially], p = 0.01) than those with mean BHL < 1.4 L. Positional errors were similar for patients with ΔBHL< 0.03 L and > 0.03 L. CONCLUSION: Under rigorous breath-hold respiratory control, BHL correlated with body weight and height. With more accurate alignment reference by stent/lipiodol, actual BHL but not breath-hold variation was associated with craniocaudal positional errors.