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1.
J Transl Med ; 22(1): 76, 2024 01 19.
Article in English | MEDLINE | ID: mdl-38243292

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a common liver malignancy with limited treatment options. Previous studies expressed the potential synergy of sorafenib and NK cell immunotherapy as a promising approach against HCC. MRI is commonly used to assess response of HCC to therapy. However, traditional MRI-based metrics for treatment efficacy are inadequate for capturing complex changes in the tumor microenvironment, especially with immunotherapy. In this study, we investigated potent MRI radiomics analysis to non-invasively assess early responses to combined sorafenib and NK cell therapy in a HCC rat model, aiming to predict multiple treatment outcomes and optimize HCC treatment evaluations. METHODS: Sprague Dawley (SD) rats underwent tumor implantation with the N1-S1 cell line. Tumor progression and treatment efficacy were assessed using MRI following NK cell immunotherapy and sorafenib administration. Radiomics features were extracted, processed, and selected from both T1w and T2w MRI images. The quantitative models were developed to predict treatment outcomes and their performances were evaluated with area under the receiver operating characteristic (AUROC) curve. Additionally, multivariable linear regression models were constructed to determine the correlation between MRI radiomics and histology, aiming for a noninvasive evaluation of tumor biomarkers. These models were evaluated using root-mean-squared-error (RMSE) and the Spearman correlation coefficient. RESULTS: A total of 743 radiomics features were extracted from T1w and T2w MRI data separately. Subsequently, a feature selection process was conducted to identify a subset of five features for modeling. For therapeutic prediction, four classification models were developed. Support vector machine (SVM) model, utilizing combined T1w + T2w MRI data, achieved 96% accuracy and an AUROC of 1.00 in differentiating the control and treatment groups. For multi-class treatment outcome prediction, Linear regression model attained 85% accuracy and an AUC of 0.93. Histological analysis showed that combination therapy of NK cell and sorafenib had the lowest tumor cell viability and the highest NK cell activity. Correlation analyses between MRI features and histological biomarkers indicated robust relationships (r = 0.94). CONCLUSIONS: Our study underscored the significant potential of texture-based MRI imaging features in the early assessment of multiple HCC treatment outcomes.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Rats , Animals , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Sorafenib/pharmacology , Sorafenib/therapeutic use , Radiomics , Rats, Sprague-Dawley , Treatment Outcome , Biomarkers, Tumor , Magnetic Resonance Imaging/methods , Killer Cells, Natural , Retrospective Studies , Tumor Microenvironment
2.
BMC Cancer ; 24(1): 1215, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39350084

ABSTRACT

BACKGROUND: Heterogeneity of hepatocellular carcinoma (HCC) presents significant challenges for therapeutic strategies and necessitates combinatorial treatment approaches to counteract suppressive behavior of tumor microenvironment and achieve improved outcomes. Here, we employed cytokines to induce memory-like behavior in natural killer (NK) cells, thereby enhancing their cytotoxicity against HCC. Additionally, we evaluated the potential benefits of combining sorafenib with this newly developed memory-like NK cell (pNK) immunochemotherapy in a preclinical model. METHODS: HCC tumors were grown in SD rats using subcapsular implantation. Interleukin 12/18 cytokines were supplemented to NK cells to enhance cytotoxicity through memory activation. Tumors were diagnosed using MRI, and animals were randomly assigned to control, pNK immunotherapy, sorafenib chemotherapy, or combination therapy groups. NK cells were delivered locally via the gastrointestinal tract, while sorafenib was administered systemically. Therapeutic responses were monitored with weekly multi-parametric MRI scans over three weeks. Afterward, tumor tissues were harvested for histopathological analysis. Structural and functional changes in tumors were evaluated by analyzing MRI and histopathology data using ANOVA and pairwise T-test analyses. RESULTS: The tumors were allowed to grow for six days post-cell implantation before treatment commenced. At baseline, tumor diameter averaged 5.27 mm without significant difference between groups (p = 0.16). Both sorafenib and combination therapy imposed greater burden on tumor dimensions compared to immunotherapy alone in the first week. By the second week of treatment, combination therapy had markedly expanded its therapeutic efficacy, resulting in the most significant tumor regression observed (6.05 ± 1.99 vs. 13.99 ± 8.01 mm). Histological analysis demonstrated significantly improved cell destruction in the tumor microenvironment associated with combination treatment (63.79%). Interestingly, we observed fewer viable tumor regions in the sorafenib group (38.9%) compared to the immunotherapy group (45.6%). Notably, there was a significantly higher presence of NK cells in the tumor microenvironment with combination therapy (34.79%) compared to other groups (ranging from 2.21 to 26.50%). Although the tumor sizes in the monotherapy groups were similar, histological analysis revealed a stronger response in pNK cell immunotherapy group compared to the sorafenib group. CONCLUSIONS: Experimental results indicated that combination therapy significantly enhanced treatment response, resulting in substantial tumor growth reduction in alignment with histological analysis.


Subject(s)
Carcinoma, Hepatocellular , Killer Cells, Natural , Liver Neoplasms , Sorafenib , Sorafenib/therapeutic use , Sorafenib/pharmacology , Animals , Killer Cells, Natural/immunology , Rats , Liver Neoplasms/therapy , Liver Neoplasms/immunology , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/drug therapy , Immunotherapy/methods , Humans , Combined Modality Therapy , Tumor Microenvironment/immunology , Tumor Microenvironment/drug effects , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/administration & dosage , Male , Niacinamide/analogs & derivatives , Niacinamide/therapeutic use , Niacinamide/pharmacology , Phenylurea Compounds/therapeutic use , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/pharmacology , Immunologic Memory/drug effects , Cell Line, Tumor , Disease Models, Animal
3.
Radiology ; 305(3): 666-671, 2022 12.
Article in English | MEDLINE | ID: mdl-35916678

ABSTRACT

Background Point-of-care (POC) MRI is a bedside imaging technology with fewer than five units in clinical use in the United States and a paucity of scientific studies on clinical applications. Purpose To evaluate the clinical and operational impacts of deploying POC MRI in emergency department (ED) and intensive care unit (ICU) patient settings for bedside neuroimaging, including the turnaround time. Materials and Methods In this preliminary retrospective study, all patients in the ED and ICU at a single academic medical center who underwent noncontrast brain MRI from January 2021 to June 2021 were investigated to determine the number of patients who underwent bedside POC MRI. Turnaround time, examination limitations, relevant findings, and potential CT and fixed MRI findings were recorded for patients who underwent POC MRI. Descriptive statistics were used to describe clinical variables. The Mann-Whitney U test was used to compare the turnaround time between POC MRI and fixed MRI examinations. Results Of 638 noncontrast brain MRI examinations, 36 POC MRI examinations were performed in 35 patients (median age, 66 years [IQR, 57-77 years]; 21 women), with one patient undergoing two POC MRI examinations. Of the 36 POC MRI examinations, 13 (36%) occurred in the ED and 23 (64%) in the ICU. There were 12 of 36 (33%) POC MRI examinations interpreted as negative, 14 of 36 (39%) with clinically significant imaging findings, and 10 of 36 (28%) deemed nondiagnostic for reasons such as patient motion. Of 23 diagnostic POC MRI examinations with comparison CT available, three (13%) demonstrated acute infarctions not apparent on CT scans. Of seven diagnostic POC MRI examinations with subsequent fixed MRI examinations, two (29%) demonstrated missed versus interval subcentimeter infarctions, while the remaining demonstrated no change. The median turnaround time of POC MRI was 3.4 hours in the ED and 5.3 hours in the ICU. Conclusion Point-of-care (POC) MRI was performed rapidly in the emergency department and intensive care unit. A few POC MRI examinations demonstrated acute infarctions not apparent at standard-of-care CT examinations. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Anzai and Moy in this issue.


Subject(s)
Emergency Service, Hospital , Point-of-Care Systems , Humans , Female , Aged , Retrospective Studies , Neuroimaging , Magnetic Resonance Imaging , Infarction , Brain/diagnostic imaging
4.
J Transl Med ; 18(1): 61, 2020 02 10.
Article in English | MEDLINE | ID: mdl-32039734

ABSTRACT

BACKGROUND: There is a lack of well-established clinical tools for predicting dendritic cell (DC) vaccination response of pancreatic ductal adenocarcinoma (PDAC). DC vaccine treatment efficiency was demonstrated using histological analysis in pre-clinical studies; however, its usage was limited due to invasiveness. In this study, we aimed to investigate the potential of MRI texture features for detection of early immunotherapeutic response as well as overall survival (OS) of PDAC subjects following dendritic cell (DC) vaccine treatment in LSL-KrasG12D;LSL-Trp53R172H;Pdx-1-Cre (KPC) transgenic mouse model of pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: KPC mice were treated with DC vaccines, and tumor growth was dynamically monitored. A total of a hundred and fifty-two image features of T2-weighted MRI images were analyzed using a kernel-based support vector machine model to detect treatment effects following the first and third weeks of the treatment. Moreover, univariate analysis was performed to describe the association between MRI texture and survival of KPC mice as well as histological tumor biomarkers. RESULTS: OS for mice in the treatment group was 54.8 ± 22.54 days while the control group had 35.39 ± 17.17 days. A subset of three MRI features distinguished treatment effects starting from the first week with increasing accuracy throughout the treatment (75% to 94%). Besides, we observed that short-run emphasis of approximate wavelet coefficients had a positive correlation with the survival of the KPC mice (r = 0.78, p < 0.001). Additionally, tissue-specific MRI texture features showed positive association with fibrosis percentage (r = 0.84, p < 0.002), CK19 positive percentage (r = - 0.97, p < 0.001), and Ki67 positive cells (r = 0.81, p < 0.02) as histological disease biomarkers. CONCLUSION: Our results demonstrate that MRI texture features can be used as imaging biomarkers for early detection of therapeutic response following DC vaccination in the KPC mouse model of PDAC. Besides, MRI texture can be utilized to characterize tumor microenvironment reflected with histology analysis.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Vaccines , Animals , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/therapy , Immunotherapy, Active , Magnetic Resonance Imaging , Mice , Mice, Transgenic , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/therapy , Tumor Microenvironment
5.
Magn Reson Med ; 84(1): 365-374, 2020 07.
Article in English | MEDLINE | ID: mdl-31850550

ABSTRACT

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.


Subject(s)
Contrast Media , Liver Neoplasms , Animals , Biomarkers , Electroporation , Liver/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Magnetic Resonance Imaging , Perfusion , Rabbits
6.
Cytotherapy ; 22(1): 6-15, 2020 01.
Article in English | MEDLINE | ID: mdl-32005355

ABSTRACT

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths with high recurrence after surgery due to a paucity of effective post-surgical adjuvant treatments. DC vaccines can activate multiple anti-tumor immune responses but have not been explored for post-surgery PDAC recurrence. Intraperitoneal (IP) delivery may allow increased DC vaccine dosage and migration to lymph nodes. Here, we investigated the role of prophylactic DC vaccination controlling PDAC tumor growth with IP delivery as an administration route for DC vaccination. METHODS: DC vaccines were generated using ex vivo differentiation and maturation of bone marrow-derived precursors. Twenty mice were divided into four groups (n = 5) and treated with DC vaccines, unpulsed mature DCs, Panc02 lysates or no treatment. After tumor induction, mice underwent three magnetic resonance imaging scans to track tumor growth. Apparent diffusion coefficient (ADC), a quantitative magnetic resonance imaging measurement of tumor microstructure, was calculated. Survival was tracked. Tumor tissue was collected after death and stained with hematoxylin and eosin, Masson's trichrome, terminal deoxynucleotidyl transferase dUTP nick end labeling and anti-CD8 stains for histology. RESULTS: DC-vaccinated mice demonstrated stronger anti-tumor cytotoxicity compared with control groups on lactate dehydrogenase assay. DC vaccine mice also demonstrated decreased tumor volume, prolonged survival and increased ΔADC compared with control groups. On histology, the DC vaccine group had increased apoptosis, increased CD8+ T cells and decreased collagen. ΔADC negatively correlated with % collagen in tumor tissues. DISCUSSION: Prophylactic DC vaccination may inhibit PDAC tumor growth during recurrence and prolong survival. ΔADC may be a potential imaging biomarker that correlates with tumor histological features.


Subject(s)
Cancer Vaccines/immunology , Carcinoma, Pancreatic Ductal/therapy , Dendritic Cells/immunology , Dendritic Cells/transplantation , Pancreatic Neoplasms/therapy , Adenocarcinoma/therapy , Animals , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor , Disease Models, Animal , Female , Humans , Lymph Nodes/cytology , Mice , Mice, Inbred C57BL , Neoplasm Recurrence, Local/prevention & control , Vaccination , Pancreatic Neoplasms
7.
AJR Am J Roentgenol ; 214(1): 137-143, 2020 01.
Article in English | MEDLINE | ID: mdl-31642697

ABSTRACT

OBJECTIVE. The purpose of this study is to retrospectively assess the impact of iterative metal artifact reduction (IMAR) with iterative reconstruction (IR) on the image quality and diagnostic performance of CT urography in the evaluation of patients with hip prostheses, compared with IR alone. MATERIALS AND METHODS. CT urography examinations that were reconstructed using IR with and without IMAR were analyzed for 57 patients (29 women and 28 men; mean age, 74 years [range, 22-94 years]) with hip prostheses (40 unilateral and 17 bilateral). For quantitative analysis, image noise within the bladder was measured. Two radiologists (radiologist 1 [RAD1] and radiologist 2 [RAD2]) qualitatively evaluated the images using both a 5-point scale to assess the degree of visualization of artifacts and a 6-point scale to determine diagnostic confidence in visualization of the bladder, ureters, prostate or uterus, pelvic calcifications, and genitourinary abnormalities involving the bladder, distal ureters, prostate, uterus, and ovaries. RESULTS. The combination of IMAR and an IR technique provided improvement in quantitative and qualitative measurements (p < 0.05). Forty-three genitourinary abnormalities were detected in 29 patients. Quantitative and qualitative comparisons of scans obtained with and without the use of IMAR, respectively, revealed image noise of 99.6 versus 173.3 HU and the following radiologist scores: for improvement of artifacts, 3.2 versus 1.6 (for RAD1) and 3.1 versus 1.6 (for RAD2); for visualization of the bladder, 3.6 versus 1.5 (RAD1) and 3.8 versus 1.6 (RAD2); visualization of the ureters, 3.8 versus 1.6 (RAD1) and 3.9 versus 1.7 (RAD2); visualization of the uterus, 4.3 versus 2.8 (RAD1) and 4.3 versus 2.6 (RAD2); visualization of the prostate, 4.5 versus 2.3 (RAD1) and 4.5 versus 2.2 (RAD2); diagnostic confidence for calcifications, 4.7 versus 3.5 (RAD1) and 4.7 versus 3.3 (RAD2); and diagnostic confidence for genitourinary abnormalities, 5.0 versus 3.2 (RAD1) and 4.8 versus 2.9 (RAD2), respectively. CONCLUSION. The addition of IMAR to IR led to statistically significant improvement in the retrospective diagnostic performance and image quality of CT urography for patients with hip prostheses, compared with IR alone.


Subject(s)
Algorithms , Artifacts , Hip Prosthesis , Image Processing, Computer-Assisted , Tomography, X-Ray Computed/methods , Urography/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Metals , Middle Aged , Retrospective Studies , Young Adult
8.
Hepatology ; 67(3): 873-883, 2018 03.
Article in English | MEDLINE | ID: mdl-28833344

ABSTRACT

Does imaging response predict survival in hepatocellular carcinoma (HCC)? We studied the ability of posttherapeutic imaging response to predict overall survival. Over 14 years, 948 patients with HCC were treated with radioembolization. Patients with baseline metastases, vascular invasion, multifocal disease, Child-Pugh > B7, and transplanted/resected were excluded. This created our homogeneous study cohort of 134 patients with Child-Pugh ≤ B7 and solitary HCC. Response (using European Association for Study of the Liver [EASL] and Response Evaluation Criteria in Solid Tumors 1.1 [RECIST 1.1] criteria) was associated with survival using Landmark and risk-of-death methodologies after reviewing 960 scans. In a subanalysis, survival times of responders were compared to those of patients with stable disease (SD) and progressive disease (PD). Uni/multivariate survival analyses were performed at each Landmark. At the 3-month Landmark, responders survived longer than nonresponders by EASL (hazard ratio [HR], 0.46; confidence interval [CI], 0.26-0.82; P = 0.002) but not RECIST 1.1 criteria (HR, 0.70; CI, 0.37-1.32; P = 0.32). At the 6-month Landmark, responders survived longer than nonresponders by EASL (HR, 0.32; CI, 0.15-0.77; P < 0.001) and RECIST 1.1 criteria (HR, 0.50; CI, 0.29-0.87; P = 0.021). At the 12-month Landmark, responders survived longer than nonresponders by EASL (HR, 0.34; CI, 0.15-0.77; P < 0.001) and RECIST 1.1 criteria (HR, 0.52; CI 0.27-0.98; P = 0.049). At 6 months, risk of death was lower for responders by EASL (P < 0.001) and RECIST 1.1 (P = 0.0445). In subanalyses, responders lived longer than patients with SD or PD. EASL response was a significant predictor of survival at 3-, 6-, and 12-month Landmarks on uni/multivariate analyses. CONCLUSION: Response to radioembolization in patients with solitary HCC can prognosticate improved survival. EASL necrosis criteria outperformed RECIST 1.1 size criteria in predicting survival. The therapeutic objective of radioembolization should be radiologic response and not solely to prevent progression. (Hepatology 2018;67:873-883).


Subject(s)
Carcinoma, Hepatocellular/therapy , Embolization, Therapeutic/methods , Liver Neoplasms/therapy , Aged , Carcinoma, Hepatocellular/mortality , Female , Humans , Liver Neoplasms/mortality , Magnetic Resonance Imaging/methods , Male , Middle Aged , Survival Analysis , Tomography, X-Ray Computed/methods , Treatment Outcome
9.
Hepatology ; 68(4): 1429-1440, 2018 10.
Article in English | MEDLINE | ID: mdl-29194711

ABSTRACT

Yttrium-90 transarterial radioembolization (TARE) is a locoregional therapy (LRT) for hepatocellular carcinoma (HCC). In this study, we present overall survival (OS) outcomes in a 1,000-patient cohort acquired over a 15-year period. Between December 1, 2003 and March 31, 2017, 1,000 patients with HCC were treated with TARE as part of a prospective cohort study. A comprehensive review of toxicity and survival outcomes was performed. Outcomes were stratified by baseline Child-Pugh (CP) class, United Network for Organ Sharing (UNOS), and Barcelona Clinic Liver Cancer (BCLC) staging systems. Albumin and bilirubin laboratory toxicities were compared to baseline. OS outcomes were reported using censoring and intention-to-treat methodologies. All treatments were outpatient, with a median one treatment per patient. Five hundred six (51%) were CP A, 450 (45%) CP B, and 44 (4%) CP C. Two hundred sixty-three (26%) patients were BCLC A, 152 (15%) B, 541 (54%) C, and 44 (4%) D. Three hundred sixty-eight (37%) were UNOS T1/T2, 169 (17%) T3, 147 (15%) T4a, 223 (22%) T4b, and 93 (9%) N/M. In CP A patients, censored OS for BCLC A was 47.3 (confidence interval [CI], 39.5-80.3) months, BCLC B 25.0 (CI, 17.3-30.5) months, and BCLC C 15.0 (CI, 13.8-17.7) months. In CP B patients, censored OS for BCLC A was 27 (CI, 21-30.2) months, BCLC B 15.0 (CI, 12.3-19.0) months, and BCLC C 8.0 (CI, 6.8-9.5) months. Forty-nine (5%) and 110 (11%) patients developed grade 3/4 albumin and bilirubin toxicities, respectively. CONCLUSION: Based on our experience with 1,000 patients over 15 years, we have made a decision to adopt TARE as the first-line transarterial LRT for patients with HCC. Our decision was informed by prospective data and incrementally reported demonstrating outcomes stratified by BCLC, applied as either neoadjuvant or definitive treatment. (Hepatology 2017).


Subject(s)
Brachytherapy/methods , Carcinoma, Hepatocellular/radiotherapy , Liver Neoplasms/radiotherapy , Yttrium Radioisotopes/therapeutic use , Adult , Aged , Analysis of Variance , Cancer Care Facilities , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Cohort Studies , Decision Making , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness/pathology , Neoplasm Staging , Radiation Injuries/prevention & control , Radiotherapy Dosage , Retrospective Studies , Risk Assessment , Survival Rate , Time Factors , Treatment Outcome , United States
10.
J Vasc Interv Radiol ; 30(11): 1863-1869, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31542271

ABSTRACT

PURPOSE: To evaluate the feasibility of diffusion-weighted imaging (DWI) in magnetic resonance imaging for quantitative measurement of responses following irreversible electroporation (IRE) in a rabbit liver tumor model. MATERIALS AND METHODS: Twelve rabbits underwent ultrasound-guided VX2 tumor implantation in the left medial and left lateral liver lobes. The tumors in the left medial lobe were treated with IRE, whereas those in the left lateral lobe served as internal controls. DWI was performed before and immediately after IRE. Tumors were then harvested for histopathologic staining. The apparent diffusion coefficient (ADC) and change in ADC (ΔADC) were calculated based on DWI. Tumor apoptosis index (AI) was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling. These measurements from DWI and histopathology were compared between untreated and treated tumors. RESULTS: The ADC values, ΔADC, and AI showed statistically significant differences between treated and untreated tumors (P < .05 for all). ADC values were higher in treated tumors than in untreated tumors (1.08 × 10-3 mm2/s ± 0.15 vs 0.88 × 10-3 mm2/s ± 0.19; P = .042). CONCLUSIONS: DWI can be used to quantitatively evaluate treatment response in liver tumors immediately after IRE.


Subject(s)
Ablation Techniques , Diffusion Magnetic Resonance Imaging , Electroporation , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Animals , Apoptosis , Cell Line, Tumor , Feasibility Studies , Liver Neoplasms/pathology , Predictive Value of Tests , Rabbits
12.
AJR Am J Roentgenol ; 212(4): 808-814, 2019 04.
Article in English | MEDLINE | ID: mdl-30673337

ABSTRACT

OBJECTIVE: The purpose of this study was to assess the performance of tin filter-based spectral shaping CT compared with routine low-dose CT for detection of urolithiasis. MATERIALS AND METHODS: Unenhanced third-generation dual-source CT scans of 129 consecutively registered patients were retrospectively reviewed: 43 patients underwent CT for detection of renal stones with tin filtration (Sn150 kV); 43 patients underwent a routine low-dose CT protocol at 100 kV; and 43 patients underwent a routine CT protocol with automated tube potential selection (110-120 kV). Image quality was evaluated subjectively and objectively. Volume CT dose index (CTDIvol) and size-specific dose estimate (SSDE) were recorded. To prospectively compare the performances of the spectral shaping protocol (Sn150 kV) with the standard (120 kV) and routine low-dose (100 kV) protocols, a phantom (sheep kidneys) containing stones were also scanned with each protocol and evaluated by two radiologists. RESULTS: CT with tin filtration resulted in 28% and 66% reduction in CTDIvol compared with CT performed with routine low-dose and standard-dose protocols (p < 0.05). Accordingly, it also led to 24% and 55% reduction in SSDE compared with the low-dose and standard protocols (p < 0.05). Subjective image quality and signal-to-noise ratio were similar between the tin filtration and the routine low-dose groups (p > 0.05). The objective image noise was similar in the three groups (p > 0.05). The phantom study showed no difference in detection of renal stones between the three tube potential settings. CONCLUSION: Using spectral shaping with tin filtration can substantially reduce radiation dose compared with routine standard- and low-dose abdominal CT for urinary stone disease.


Subject(s)
Tomography, X-Ray Computed/methods , Urinary Calculi/diagnostic imaging , Adult , Aged , Animals , Female , Humans , Male , Middle Aged , Phantoms, Imaging , Radiation Dosage , Radiation Protection/methods , Retrospective Studies , Sheep , Tin
13.
Radiographics ; 39(2): 388-412, 2019.
Article in English | MEDLINE | ID: mdl-30707646

ABSTRACT

Intraluminal pathologic conditions of the bile ducts and gallbladder are common, most frequently consisting of calculi and adenocarcinoma. In recent years, intraductal papillary neoplasm of the bile ducts (IPN-B), which is analogous to intraductal papillary mucinous neoplasm of the pancreas, has been recognized as a distinct pathologic entity and a precursor lesion to adenocarcinoma of the bile ducts. Intraductal tubulopapillary neoplasm (ITPN) of the bile duct was subsequently described as a distinct pathologic entity. With increased awareness and advances in imaging techniques, these lesions are diagnosed with increased frequency at preoperative imaging. A similar neoplasm in the gallbladder is referred to as intracholecystic papillary neoplasm. These lesions are often diagnosed at a preinvasive stage and have a better prognosis than invasive cholangiocarcinoma when treated with curative resection, underscoring the importance of an accurate imaging diagnosis. The most common causes of polypoid lesions of the gallbladder are cholesterol polyps and adenomyomatosis. These lesions need to be differentiated from the less common but clinically important adenocarcinoma of the gallbladder. Imaging is crucial to identify polyps that are at high risk for malignancy so that the appropriate management choice between imaging follow-up and cholecystectomy can be made by the treating physicians. Other less common gallbladder tumors, such as gallbladder adenomas, lymphoma, and metastases to the gallbladder, can manifest as intraluminal tumors; and awareness of these lesions is also important. In this article, the recent literature is reviewed; and the imaging appearances, histopathologic findings, and management of uncommon intraluminal tumors of the bile ducts and gallbladder and their mimics are discussed. ©RSNA, 2019.


Subject(s)
Bile Duct Neoplasms/diagnostic imaging , Carcinoma, Papillary/diagnostic imaging , Gallbladder Neoplasms/diagnostic imaging , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Adenoma/diagnostic imaging , Bile Duct Neoplasms/pathology , Carcinoma, Papillary/pathology , Diagnosis, Differential , Female , Gallbladder Diseases/diagnostic imaging , Gallbladder Neoplasms/pathology , Humans , Male , Risk Factors
14.
Emerg Radiol ; 26(6): 609-614, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31352639

ABSTRACT

PURPOSE: To assess the feasibility of implementing fully automated computer-aided diagnosis (CAD) for detection of pulmonary nodules on CT pulmonary angiography (CTPA) studies in emergency setting. MATERIALS AND METHODS: CTPA of 48 emergency patients was retrospectively reviewed. Fully automated CAD nodule detection was performed at the scanner and results were automatically submitted to PACS. A third-year radiology resident (RAD1) and a cardiothoracic radiologist with 6 years' experience (RAD2) reviewed the scans independently to detect pulmonary nodules in two different sessions 8 weeks apart: session 1, CAD was reviewed first and then all images were reviewed; session 2, CAD was reviewed last after all images were reviewed. Time spent by RAD to evaluate image sets was measured for each case. Fisher's exact test and t test were used. RESULTS: There were 17 male and 31 female patients with mean ± SD age of 48.7 ± 16.4 years. Using CAD at the beginning was associated with lower average reading time for both readers. However, difference in reading time did not reach statistical significance for RAD1 (RAD1 94.6 s vs. 102.7 s, P > 0.05; RAD2 61.1 s vs. 76.5 s, P < 0.05). Using CAD at the end significantly increased rate of RAD1 and RAD2 nodule detection by 34% (2.52 vs. 2.12 nodule/scan, P < 0.05) and 27% (2.23 vs. 1.81 nodule/scan, P < 0.05), respectively. CONCLUSION: Routine utilization of CAD in emergency setting is feasible and can improve detection rate of pulmonary nodules significantly. Different methods of incorporating CAD in detecting pulmonary nodules can improve both the rate of detection and interpretation speed.


Subject(s)
Computed Tomography Angiography , Emergency Service, Hospital , Lung Neoplasms/diagnostic imaging , Radiographic Image Interpretation, Computer-Assisted/methods , Solitary Pulmonary Nodule/diagnostic imaging , Workflow , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Feasibility Studies , Female , Humans , Male , Middle Aged , Retrospective Studies
15.
Radiology ; 287(1): 137-145, 2018 04.
Article in English | MEDLINE | ID: mdl-29232185

ABSTRACT

Purpose To test the hypothesis that biomarkers of fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used for the early detection of therapeutic response to irreversible electroporation (IRE) of liver tumor in a rodent liver tumor model. Materials and Methods The institutional animal care and use committee approved this study. Rats were inoculated with McA-RH7777 liver tumor cells in the left median and left lateral lobes. Tumors were allowed to grow for 7 days to reach a size typically at least 5 mm in longest diameter, as verified with magnetic resonance (MR) imaging. IRE electrodes were inserted, and eight 100-µsec, 2000-V pulses were applied to ablate the tumor tissue in the left median lobe. Tumor in the left lateral lobe served as a control in each animal. PET/computed tomography (CT) and MR imaging measurements were performed at baseline and 3 days after IRE for each animal. Additional MR imaging measurements were obtained 14 days after IRE. After 14-day follow-up MR imaging, rats were euthanized and tumors harvested for hematoxylin-eosin, CD34, and caspase-3 staining. Change in the maximum standardized uptake value (ΔSUVmax) was calculated 3 days after IRE. The maximum lesion diameter change (ΔDmax) was measured 14 days after IRE by using axial T2-weighted imaging. ΔSUVmax and ΔDmax were compared. The apoptosis index was calculated by using caspase-3-stained slices of apoptotic tumor cells. Pearson correlation coefficients were calculated to assess the relationship between ΔSUVmax at 3 days and ΔDmax (or apoptosis index) at 14 days after IRE treatment. Results ΔSUVmax, ΔDmax, and apoptosis index significantly differed between treated and untreated tumors (P < .001 for all). In treated tumors, there was a strong correlation between ΔSUVmax 3 days after IRE and ΔDmax 14 days after IRE (R = 0.66, P = .01) and between ΔSUVmax 3 days after IRE and apoptosis index 14 days after IRE (R = 0.57, P = .04). Conclusion 18F-FDG PET imaging biomarkers can be used for the early detection of therapeutic response to IRE treatment of liver tumors in a rodent model. © RSNA, 2017.


Subject(s)
Electroporation/methods , Fluorodeoxyglucose F18 , Liver Neoplasms/metabolism , Liver Neoplasms/therapy , Positron-Emission Tomography/methods , Radiopharmaceuticals , Animals , Biomarkers/metabolism , Disease Models, Animal , Liver/diagnostic imaging , Liver/metabolism , Liver Neoplasms/diagnostic imaging , Rats , Treatment Outcome
16.
AJR Am J Roentgenol ; 210(4): 715-719, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29412016

ABSTRACT

OBJECTIVE: The objective or our study was to assess the incidence rate and clinical characteristics of allergiclike reactions in patients who received both nonionic iodinated contrast medium (ICM) and gadolinium-based contrast medium (GBCM). MATERIALS AND METHODS: Acute allergiclike reactions in patients who received both ICM and GBCM to nonionic ICM or GBCM injections during a 5-year period were analyzed. Allergy preparation was not administered when patients received a different type of contrast material. Acute allergiclike reactions to both ICM and GBCM were evaluated. RESULTS: Of 302,858 contrast injections (155,234 ICM and 147,624 GBCM) during a 5-year period, 1006 (752 ICM and 254 GBCM) acute allergiclike contrast reactions were reported. The overall rate of reaction to ICM was 0.48% (95% CI, 0.45-0.52%), and the overall rate of reaction to GBCM was 0.17% (95% CI, 0.15-0.19%). A total of 19,237 patients received at least one ICM injection and one GBCM injection, with a total of 56,310 injections (19,237 initial injections and 37,073 subsequent injections). Nine patients had reactions to both ICM and GBCM with the primary reaction rate of 9/19,237 (incidence rate, 0.047%; 95% CI, 0.044-0.050%), and the secondary reaction rate of 9/37,073 (incidence rate, 0.024%; 95% CI, 0.023-0.026%). All secondary reactions in patients who had a reaction to both ICM and GBCM were mild. None of the patients required medication for the treatment of the secondary reaction. CONCLUSION: An allergiclike reaction to both nonionic ICM and GBCM was an extremely rare event that presented as a mild acute reaction without significant clinical consequences despite the fact that an allergy preparation was not administered.


Subject(s)
Contrast Media/adverse effects , Drug Hypersensitivity/epidemiology , Gadolinium/adverse effects , Iodine/adverse effects , Adult , Aged , Aged, 80 and over , Female , Gadolinium DTPA/adverse effects , Humans , Incidence , Male , Meglumine/adverse effects , Meglumine/analogs & derivatives , Middle Aged , Organometallic Compounds/adverse effects , Retrospective Studies , Risk Factors
17.
AJR Am J Roentgenol ; 211(6): 1234-1245, 2018 12.
Article in English | MEDLINE | ID: mdl-30240294

ABSTRACT

OBJECTIVE: The objective of this study was to determine whether quantitative texture analysis of MR images would improve the ability to distinguish papillary renal cell carcinoma (RCC) subtypes, compared with analysis of qualitative MRI features alone. MATERIALS AND METHODS: A total of 47 pathologically proven papillary RCC tumors were retrospectively evaluated, with 31 (66%) classified as type 1 tumors and 16 (34%) classified as type 2 tumors. MR images were reviewed by two readers to determine tumor size, signal intensity, heterogeneity, enhancement pattern, margins, perilesional stranding, vein thrombosis, and metastasis. Quantitative texture analysis of gray-scale images was performed. A logistic regression was derived from qualitative and quantitative features. Model performance was compared with and without texture features. RESULTS: The significant qualitative MR features noted were necrosis, enhancement appearance, perilesional stranding, and metastasis. A multivariable model based on qualitative features did not identify any factor as an independent predictor of a type 2 tumor. The logistic regression model for predicting papillary RCCs on the basis of qualitative and quantitative analysis identified probability of the 2D volumetric interpolated breath-hold examination (VIBE) sequence (AUC value, 0.87; 95% CI, 0.77-0.98) as an independent predictor of a type 2 tumor. No difference in the model AUC value was noted when texture features were included in the analysis; however, the model had increased sensitivity and an improved predictive value without loss of specificity. CONCLUSION: The addition of texture analysis to analysis of conventional qualitative MRI features increased the probability of predicting a type 2 papillary RCC tumor, which may be clinically important.


Subject(s)
Carcinoma, Renal Cell/diagnostic imaging , Imaging, Three-Dimensional , Kidney Neoplasms/diagnostic imaging , Magnetic Resonance Imaging , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/pathology , Diagnosis, Differential , Female , Humans , Kidney Neoplasms/pathology , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity
18.
Gastroenterology ; 151(6): 1155-1163.e2, 2016 12.
Article in English | MEDLINE | ID: mdl-27575820

ABSTRACT

BACKGROUND & AIMS: Conventional transarterial chemoembolization (cTACE) is used to treat patients with hepatocellular carcinoma (HCC). Radioembolization is a minimally invasive procedure that involves implantation of radioactive micron-sized particles loaded with yttrium-90 (Y90) inside the blood vessels that supply a tumor. We performed a randomized, phase 2 study to compare the effects of cTACE and Y90 radioembolization in patients with HCC. METHODS: From October 2009 through October 2015, we reviewed patients with HCC of all Barcelona Clinic Liver Cancer (BCLC) stages for eligibility. Of these, 179 patients with BCLC stages A or B met our enrollment criteria and were candidates for cTACE or Y90 therapy. Patients were assigned randomly to groups that received Y90 therapy (n = 24; 50% Child-Pugh A) or cTACE (n = 21; 71% Child-Pugh A). The primary outcome was time to progression (TTP), evaluated by intention-to-treat analysis. Secondary outcomes included safety, rate of response (based on tumor size and necrosis criteria), and Kaplan-Meier survival time. We performed inverse probability of censoring weighting and competing risk analyses. RESULTS: Patients in the Y90 radioembolization group had significant longer median TTP (>26 mo) than patients in the cTACE group (6.8 mo; P = .0012) (hazard ratio, 0.122; 95% confidence interval [CI], 0.027-0.557; P = .007). This was confirmed by competing risk and inverse probability of censoring weighting analyses accounting for transplantation or death. A significantly greater proportion of patients in the cTACE group developed diarrhea (21%) than in the Y90 group (0%; P = .031) or hypoalbuminemia (58% in the cTACE group vs 4% in the Y90 group; P < .001). Similar proportions of patients in each group had a response to therapy, marked by necrosis (74% in the cTACE group vs 87% in the Y90 group) (P = .433). The median survival time, censored to liver transplantation, was 17.7 months for the cTACE group (95% CI, 8.3-not calculable) vs 18.6 months for the Y90 group (95% CI, 7.4-32.5) (P = .99). CONCLUSIONS: In a randomized phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce drop-out from transplant waitlists. ClinicalTrials.gov no. NCT00956930.


Subject(s)
Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Yttrium Radioisotopes/therapeutic use , Aged , Antineoplastic Agents/therapeutic use , Chemoembolization, Therapeutic/adverse effects , Diarrhea/etiology , Disease Progression , Disease-Free Survival , Ethiodized Oil/therapeutic use , Female , Humans , Hypoalbuminemia/etiology , Intention to Treat Analysis , Liver Transplantation , Male , Middle Aged , Necrosis , Neoplasm Staging , Prospective Studies , Survival Rate , Yttrium Radioisotopes/adverse effects
20.
J Vasc Interv Radiol ; 28(11): 1520-1526, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28673658

ABSTRACT

PURPOSE: To determine long-term hepatotoxicity of yttrium-90 (90Y) radioembolization in patients treated for metastatic neuroendocrine tumor (mNET) and evaluate if imaging and laboratory findings of cirrhosis-like morphology are associated with clinical symptoms. MATERIALS AND METHODS: Retrospective review from 2003 to 2016 was performed for patients with mNET treated with 90Y glass microspheres. Fifty-four patients with > 2 year follow-up were stratified into unilobar (n = 15) vs whole-liver (n = 39) treatment. The most common primary mNET sites were small bowel (19 of 54), pancreas (19 of 54), and unknown (8 of 54). Preradioembolization imaging and laboratory findings were compared with most recent follow-up for indications of worsening portal hypertension and decline in hepatic function. RESULTS: Among patients who underwent unilobar radioembolization, imaging follow-up at a mean of 4.1 years (range, 2.0-15.2 y) revealed cirrhosis-like morphology in 26.7% (4 of 15), ascites in 13.3% (2 of 15), varices in 6.7% (1 of 15), and a 21.9% increase in splenic volume. The respective incidences in patients treated with whole-liver 90Y radioembolization were 56.4% (22 of 39), 41.0% (16 of 39), and 15.4% (6 of 39), with a 64.7% increase in splenic volume. Patients treated with whole-liver radioembolization exhibited significantly decreased platelet counts (P = .023) and lower albumin levels (P = .0002). Eight patients (20.5%) treated with whole-liver radioembolization who exhibited cirrhosis-like morphology showed clinical signs of hepatic decompensation; only 2 of 39 patients (5.1%) had no other causes of hepatotoxicity. CONCLUSIONS: Whole-liver 90Y radioembolization for patients with mNET results in long-term imaging findings of cirrhosis-like morphology and portal hypertension in > 50% of treated patients, but the majority remain clinically asymptomatic. Long-term hepatotoxicity solely attributable to 90Y develops in a small percentage of patients.


Subject(s)
Embolization, Therapeutic/adverse effects , Liver Neoplasms/radiotherapy , Liver Neoplasms/secondary , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/radiotherapy , Yttrium Radioisotopes/adverse effects , Adult , Aged , Aged, 80 and over , Disease Progression , Female , Humans , Male , Middle Aged , Radiation Dosage , Radiology, Interventional , Retrospective Studies , Treatment Outcome
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