NCTN Assessment on Current Applications of Radiomics in Oncology.

Radiomics is a fast-growing research area based on converting standard-of-care imaging into quantitative minable data and building subsequent predictive models to personalize treatment. Radiomics has been proposed as a study objective in clinical trial concepts and a potential biomarker for stratifying patients across interventional treatment arms. In recognizing the growing importance of radiomics in oncology, a group of medical physicists and clinicians from NRG Oncology reviewed the current status of the field and identified critical issues, providing a general assessment and early recommendations for incorporation in oncology studies.

Assessment of chicken breast meat quality after freeze/thaw abuse using magnetic resonance imaging techniques.

BACKGROUND: Freezing/thawing meat can result in quality losses as a result of the formation, melting and reformation of ice. These changes in water state can result in alterations in texture, water holding and other key quality attributes. It was hypothesized that magnetic resonance imaging (MRI) could quantify changes in mobility and localization of water as a function of freezing/thawing, which could be correlated with quality measurements. RESULTS: Drip loss increased significantly for unbrined samples by over 100% after each freeze/thaw cycle (1.5% to 3.3% to 5.3% drip loss). Brine uptake decreased 50% after 2 cycles (from 53% to 28% mass uptake). Drip loss for brined samples increased after 2 cycles; other attributes were not significantly affected. MRI showed brined samples had less change in both proton density and T2 distributions. High-field nuclear magnetic resonance (NMR) imaging showed greater change in T2 distributions. CONCLUSION: As freeze/thaw damage increased, meat quality was reduced in both brined and unbrined chicken breasts, with more prominent changes in unbrined meat. These decreases in quality correlated with changes, albeit small, in water mobility and localization as measured by MRI. High-field NMR micro-imaging showed more dramatic changes in T2 distributions in unbrined samples. These MRI techniques are shown to be useful in the assessment of meat quality after freeze/thaw abuse. © 2018 Society of Chemical Industry.

Quantitative Assessment of Heterogeneity in Bladder Tumor MRI Diffusivity: Can Response be Predicted Prior to Neoadjuvant Chemotherapy?

BACKGROUND: It is a critical unmet need to predict chemosensitivity in muscle-invasive bladder cancer patients who receive neoadjuvant chemotherapy (NAC). Quantification of tumor heterogeneity has been shown to be useful in the assessment of therapeutic response. Apparent diffusion coefficient (ADC) is derived from diffusion weighted MRI (DWI) to quantify the water diffusivity which characterizes micro-cellularity in tumor tissues. OBJECTIVE: The aim of this study is to assess if a quantitative measurement of ADC heterogeneity in bladder tumors can be a predictor of therapeutic response to NAC. MATERIALS AND METHODS: Twenty patients with pT2 bladder cancer have been included in this study. Patient MRI was performed on a 3T system with DWI prior to NAC. Regions of interest (ROIs) were placed over the whole tumor volume on ADC maps to acquire a data matrix of voxel-wise ADC values for each patient. We performed histogram analysis on each ADC data matrix to calculate uniformity (U) and entropy (E). These quantities were subsequently correlated with the patient's response to chemotherapy. Statistical significance was found with P < 0.05. RESULTS: Fifteen patients were categorized as responders, and five as non-responders. The data showed that tumors of responders were significantly higher in U (P = 0.01) and lower in E (P < 0.01) than non-responders. This finding indicates that resistant tumors were more heterogeneous in their spatial distribution of ADC values. While this difference in ADC heterogeneity was not always visually recognizable, it could be quantified by the data analytics. CONCLUSIONS: This study demonstrates that the quantitative readout of tumor heterogeneity in micro-cellularity is associated with the patient's defined response to chemotherapy. Quantification of tumor ADC heterogeneity may provide useful information to enable the prediction of chemotherapeutic response prior to the treatment to improve patient outcomes.

A comparison of FLT to FDG PET/CT in the early assessment of chemotherapy response in stages IB-IIIA resectable NSCLC.

BACKGROUND: The aim of this study was to compare the percentage change in 18F-fluorothymidine (FLT) standard uptake value (SUV) between baseline and after one cycle of chemotherapy in patients categorized by RECIST 1.1 computed tomography (CT) as responders or non-responders after two cycles of therapy. Change in 18F-fluorodeoxyglucose (FDG) uptake was also compared between these time points. Nine patients with newly diagnosed, operable, non-small cell lung cancer (NSCLC) were imaged with FDG positron emission tomography/CT (PET), FLT PET/CT, and CT at baseline, following one cycle of neoadjuvant therapy (75 mg/m2 docetaxel + 75 mg/m2 cisplatin), and again after the second cycle of therapy. All patients had a biopsy prior to enrollment and underwent surgical resection within 4 weeks of post-cycle 2 imaging. RESULTS: Between baseline and post-cycle 1, non-responders had mean SULmax (maximum standard uptake value adjusted for lean body mass) increases of 7.0 and 3.4% for FDG and FLT, respectively. Responders had mean decreases of 44.8 and 32.0% in FDG and FLT SULmax, respectively, between baseline and post-cycle 1 imaging. On post-cycle 1 imaging, primary tumor FDG SUL values were significantly lower in responders than in non-responders (P = 0.016). Primary tumor FLT SUL values did not differ significantly between these groups. Using the change from baseline to post-cycle 1, receiver-operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.94 for FDG and 0.78 for FLT in predicting anatomic tumor response after the second cycle of therapy. CONCLUSIONS: Fractional decrease in FDG SULmax from baseline to post-cycle 1 imaging was significantly different between anatomic responders and non-responders, while percentage changes in FLT SULmax were not significantly different between these groups over the same period of time.

Is magnetic resonance imaging assessment of the size of articular cartilage defects accurate?

The purpose of this study was to systematically review the literature relative to the following question: Is preoperative magnetic resonance imaging (MRI) an accurate instrument for the assessment of the size of knee articular cartilage defects compared with arthroscopy? A systematic search was performed in September 2011 using PubMed MEDLINE (from 1966), CINAHL (from 1982), SPORTDiscus (from 1985), SCOPUS (from 1996), and EMBASE (from 1974) databases. Four studies (one study of Level II and three studies of Level III) were identified that met the predetermined inclusion and exclusion criteria. The ability of MRI to preoperatively assess the size of cartilage lesions was highly variable. As a result of inconsistencies between imaging techniques, the methodological variability and shortcomings of the studies, and the limited amount of data available, a meta-analysis was not performed. There is some evidence that MRI is an accurate tool for preoperatively assessing the dimensions of articular cartilage defects. However, because of the heterogeneity of MRI sequences and the paucity of literature related to preoperative sizing, it is not possible to make definitive conclusions regarding the global clinical utility of MRI for guiding the selection of therapeutic strategies.

RF-related heating assessment of extracranial neurosurgical implants at 7T.

PURPOSE: The purpose was to evaluate radiofrequency (RF)-related heating of commonly used extracranial neurosurgical implants in 7-T magnetic resonance imaging (MRI). MATERIALS AND METHODS: Experiments were performed using a 7-T MR system equipped with a transmit/receive RF head coil. Four commonly used titanium neurosurgical implants were studied using a test procedure adapted from the American Society for Testing and Materials Standard F2182-11a. Implants (n=4) were tested with an MRI turbo spin echo pulse sequence designed to achieve maximum RF exposure [specific absorption rate (SAR) level=9.9W/kg], which was further validated by performing calorimetry. Maximum temperature increases near each implant's surface were measured using fiberoptic temperature probes in a gelled-saline-filled phantom that mimicked the conductive properties of soft tissue. Measurement results were compared to literature data for patient safety. RESULTS: The highest achievable phantom averaged SAR was determined by calorimetry to be 2.0±0.1W/kg due to the highly conservative SAR estimation model used by this 7-T MR system. The maximum temperature increase at this SAR level was below 1.0°C for all extracranial neurosurgical implants that underwent testing. CONCLUSION: The findings indicated that RF-related heating under the conditions used in this investigation is not a significant safety concern for patients with the particular extracranial neurosurgical implants evaluated in this study.

Quantitative assessment of mobile protein levels in human knee synovial fluid: feasibility of chemical exchange saturation transfer (proteinCEST) MRI of osteoarthritis.

PURPOSE: To establish the feasibility of chemical exchange saturation transfer (proteinCEST) MRI in the differentiation of osteoarthritis (OA) knee joints from non-OA joints by detecting mobile protein and peptide levels in synovial fluid by determining their relative distribution. MATERIALS AND METHODS: A total of 25 knees in 11 men and 12 women with knee injuries were imaged using whole knee joint proteinCEST MRI sequence at 3 T. The joint synovial fluid was segmented and the asymmetric magnetization transfer ratio at 3.5 ppm MTR(asym) (3.5 ppm) was calculated to assess protein content in the synovial fluid. The 85th percentile of synovial fluid MTR(asym) (3.5 ppm) distribution profile was compared using the independent Student's t test. The diagnostic performance of the 85th percentile of synovial fluid MTR(asym) (3.5 ppm) in differentiating OA and non-OA knee joints was evaluated. RESULTS: The 85th percentile of synovial fluid MTR(asym) (3.5 ppm) in knee joints with OA was 8.6%±3.4% and significantly higher than that in the knee joints without OA (6.3%±1.4%, P<.05). A knee joint with an 85th percentile of synovial fluid MTR(asym) (3.5 ppm) greater than 7.7% was considered to be an OA knee joint. With the threshold, the sensitivity, specificity and overall accuracy for differentiating knee joints with OA from the joints without OA were 54% (7/13), 92% (11/12) and 72% (18/25), respectively. CONCLUSION: proteinCEST MRI appears feasible as a quantitative methodology to determine mobile protein levels in synovial fluid and identify patterns characteristic for OA disease.

Simulation and assessment of cerebrovascular damage in deep brain stimulation using a stereotactic atlas of vasculature and structure derived from multiple 3- and 7-tesla scans.

OBJECT: The most severe complication of deep brain stimulation (DBS) is intracranial hemorrhage. Detailed knowledge of the cerebrovasculature could reduce the rate of this disorder. Morphological scans typically acquired in stereotactic and functional neurosurgery (SFN) by using 1.5-T (or sometimes even 3-T) imaging units poorly depict the vasculature. Advanced angiographic imaging, including 3- and 7-T 3D time-of-flight and susceptibility weighted imaging as well as 320-slice CT angiography, depict the vessels in great detail. However, these acquisitions are not used in SFN clinical practice, and robust methods for their processing are not available yet. Therefore, the authors proposed the use of a detailed 3D stereotactic cerebrovascular atlas to assist in SFN planning and to potentially reduce DBS-induced hemorrhage. METHODS: A very detailed 3D cerebrovascular atlas of arteries, veins, and dural sinuses was constructed from multiple 3- and 7-T scans. The atlas contained>900 vessels, each labeled with a name and diameter with the smallest having a 90-µm diameter. The cortical areas, ventricular system, and subcortical structures were fully segmented and labeled, including the main stereotactic target structures: subthalamic nucleus, ventral intermediate nucleus of the thalamus, and internal globus pallidus. The authors also developed a computer simulator with the embedded atlas that was able to compute the effective electrode trajectory by minimizing penetration of the cerebrovascular system and vital brain structures by a DBS electrode. The simulator provides the neurosurgeon with functions for atlas manipulation, target selection, trajectory planning and editing, 3D display and manipulation, and electrode-brain penetration calculation. RESULTS: This simulation demonstrated that a DBS electrode inserted in the middle frontal gyrus may intersect several arteries and veins including 1) the anteromedial frontal artery of the anterior cerebral artery as well as the prefrontal artery and the precentral sulcus artery of the middle cerebral artery (range of diameters 0.4-0.6 mm); and 2) the prefrontal, anterior caudate, and medullary veins (range of diameters 0.1-2.3 mm). This work also shows that field strength and pulse sequence have a substantial impact on vessel depiction. The numbers of 3D vascular segments are 215, 363, and 907 for 1.5-, 3-, and 7-T scans, respectively. CONCLUSIONS: Inserting devices into the brain during microrecording and stimulation may cause microbleeds not discernible on standard scans. A small change in the location of the DBS electrode can result in a major change for the patient. The described simulation increases the neurosurgeon's awareness of this phenomenon. The simulator enables the neurosurgeon to analyze the spatial relationships between the track and the cerebrovasculature, ventricles, subcortical structures, and cortical areas, which allows the DBS electrode to be placed more effectively, and thus potentially reducing the invasiveness of the stimulation procedure for the patient.

Improvement in the reproducibility of region of interest using an auditory feedback loop: a pilot assessment using dynamic contrast-enhanced (DCE) breast MR images.

PURPOSE: To augment traditional visual data perception of complex multiparametric imaging data sets by adding auditory feedback to improve the delineation of regions of interest (ROIs) in tumor assessment in dynamic contrast-enhanced (DCE) MRI. MATERIALS AND METHODS: In addition to conventional display methodologies, we have created an application window which interfaces with audio output using dynamically loadable sound modules, providing goodness of fit (GF) information through auditory feedback. We have assessed effectiveness of conveying sound information with three independent readers on eight DCE-MR breast image data sets. The assessment was based on either conventional visual only mode or combined visual plus auditory mode. For statistical comparison between two sensory approaches, interobserver repeatability was measured with three different criteria. RESULTS: Adding auditory feedback improves repeatability significantly (P < 0.01), and the enhanced sensory approach had higher repeatability than visual only mode in visually complex breast tumor cases. However, in easy and moderate cases, visual only mode was more reproducible than the combined mode with very high significance (P < 0.001). CONCLUSION: Adding auditory information to visual based image analysis for identifying tumor ROIs provides higher interobserver repeatability for analyzing complex multidimensional/multiparametric medical image data sets with visually difficult lesions to delineate.

Combined use of preoperative 18F FDG-PET imaging and intraoperative gamma probe detection for accurate assessment of tumor recurrence in patients with colorectal cancer.

BACKGROUND: The purpose of this study was to combine intraoperative gamma probe (GP) detection with preoperative fluorine 18-fluoro-2-deoxy-glucose positron emission tomography (18F FDG-PET) imaging in order to improve detection of tumor recurrence in colorectal cancer (CRC) patients. METHODS: Twenty-one patients (12 females, 9 males) with a mean age of 54 years (range 31-78) were enrolled. Patients were suspected to have recurrent CRC by elevated CEA (n = 11), suspicious CT findings (n = 1), and clinically suspicious findings (n = 9). Preoperative FDG-PET scan and intraoperative GP study were performed in all patients. Mean time interval between preoperative FDG-PET scan and surgery was 16 days (range 1-41 days) in 19 patients. For intraoperative GP studies, 19 patients were injected with a dose of 10-15 mCi 18F FDG at approximately 30 minutes before the planned surgery time. In two patients, the intraoperative GP study was performed immediately after preoperative FDG-PET scan. RESULTS: Preoperative FDG-PET and intraoperative GP detected 48 and 45 lesions, respectively. A total of 50 presumed site of recurrent disease from 20 patients were resected. Thirty-seven of 50 presumed sites of recurrent disease were histological-proven tumor positive and 13 of 50 presumed sites of recurrent disease were histological-proven tumor negative. When correlated with final histopathology, the number of true positive lesions and false positive lesions by preoperative FDG-PET and intraoperative GP were 31/9 and 35/8, respectively. Both preoperative FDG-PET and intraoperative GP were true positive in 29 lesions. Intraoperative GP detected additional small lesions in the omentum and pelvis which were not seen on preoperative FDG-PET scan. FDG-PET scan demonstrated additional liver metastases which were not detected by intraoperative GP. Preoperative FDG-PET detected distant metastasis in the lung in one patient. The estimated radiation dose received by a surgeon during a single 18F FDG GP surgery was below the occupational limit. CONCLUSION: The combined use of preoperative FDG-PET and intraoperative GP is potentially helpful to the surgeon as a roadmap for accurately locating and determining the extent of tumor recurrence in patients with CRC. While intraoperative GP appears to be more sensitive in detecting the extent of abdominal and pelvic recurrence, preoperative FDG-PET appears to be more sensitive in detecting liver metastases. FDG-PET is also a valuable method in detecting distant metastases.

Evaluation of intraaxial enhancing brain tumors on magnetic resonance imaging: intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for visualization and assessment, and implications for surgical intervention.

OBJECT: The goal in this article was to compare 0.1 mmol/kg doses of gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine, also known as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), for enhanced magnetic resonance (MR) imaging of intraaxial brain tumors. METHODS: Eighty-four patients with either intraaxial glioma (47 patients) or metastasis (37 patients) underwent two MR imaging examinations at 1.5 tesla, one with Gd-BOPTA as the contrast agent and the other with Gd-DTPA. The interval between fully randomized contrast medium administrations was 2 to 7 days. The T1-weighted spin echo and T2-weighted fast spin echo images were acquired before administration of contrast agents and T1-weighted spin echo images were obtained after the agents were administered. Acquisition parameters and postinjection acquisition times were identical for the two examinations in each patient. Three experienced readers working in a fully blinded fashion independently evaluated all images for degree and quality of available information (lesion contrast enhancement, lesion border delineation, definition of disease extent, visualization of the lesion's internal structures, global diagnostic preference) and quantitative enhancement (that is, the extent of lesion enhancement after contrast agent administration compared with that seen before its administration [hereafter referred to as percent enhancement], lesion/brain ratio, and contrast/noise ratio). Differences were tested with the Wilcoxon signed-rank test. Reader agreement was assessed using kappa statistics. Significantly better diagnostic information/imaging performance (p < 0.0001, all readers) was obtained with Gd-BOPTA for all visualization end points. Global preference for images obtained with Gd-BOPTA was expressed for 42 (50%), 52 (61.9%), and 56 (66.7%) of 84 patients (readers 1, 2, and 3, respectively) compared with images obtained with Gd-DTPA contrast in four (4.8%), six (7.1%), and three (3.6%) of 84 patients. Similar differences were noted for all other visualization end points. Significantly greater quantitative contrast enhancement (p < 0.04) was noted after administration of Gd-BOPTA. Reader agreement was good (kappa > 0.4). CONCLUSIONS: Lesion visualization, delineation, definition, and contrast enhancement are significantly better after administration of 0.1 mmol/kg Gd-BOPTA, potentially allowing better surgical planning and follow up and improved disease management.

Dynamic contrast-enhanced MRI of malignant pleural mesothelioma: a feasibility study of noninvasive assessment, therapeutic follow-up, and possible predictor of improved outcome.

STUDY OBJECTIVE: Dynamic contrast-enhanced MRI (DCE-MRI) followed by pharmacokinetic analysis has been successfully used in a variety of solid tumors. The aims of this study were to evaluate the feasibility of DCE-MRI in malignant pleural mesothelioma (MPM), to differentiate benign from pathologic tissue and compare pharmacokinetic with clinical parameters and survival in order to map out its microcirculation; and to compare pharmacokinetic with clinical parameter and survival in order to improve our understanding of the in vivo biology of this malignancy. METHODS: Nineteen patients with a diagnosis of MPM who were scheduled to receive chemotherapy with gemcitabine were enrolled in the study. DCE-MRI was performed before treatment (n = 19) and after the third cycle (n = 12) and sixth cycle (n = 7) of chemotherapy. An established pharmacokinetic two-compartment model was used to analyze DCE-MRI. Tumor regions were characterized by the pharmacokinetic parameters amplitude (Amp), redistribution rate constant (kep), and elimination rate constant (kel). Kinetic parameters of tumor tissue and normal tissue were compared using the Student t test. Patients were classified as clinical responders or nonresponders according to clinical outcome, and these groups were compared with the pharmacokinetic parameters derived from DCE-MRI. RESULTS: Normal and tumor tissue could be distinguished by the pharmacokinetic parameters Amp and kel (p

Assessment of utilization and pharmacovigilance based on spontaneous adverse event reporting of gadopentetate dimeglumine as a magnetic resonance contrast agent after 45 million administrations and 15 years of clinical use.

PURPOSE: Although contrast agents have become indispensable tools in magnetic resonance and their safe and effective use the foundation of many essential diagnostic procedures, only limited summary information on their utilization and pharmacovigilance is available to the community. After voluntary access to the manufacturer spontaneous adverse event database, we assessed the available data for gadopentetate dimeglumine. MATERIAL AND METHODS: Gadopentetate dimeglumine (Gd-DTPA, Magnevist; Berlex/Schering AG, Berlin, Germany) became commercially available in 1988 and is currently marketed in 101 countries. Using the manufacturer's continuous and cumulative database on product distribution and spontaneous adverse event (AE) reporting, we categorized AEs and assessed their cumulative occurrence after 10, 20, and 45 million applications that occurred in 1993, 1997, and 2002, respectively. Furthermore, we reviewed publications in Medline to assess prevalence of the 4 most common MR contrast agents in the indexed literature. RESULTS: Gd-DTPA has been used in more than 45 million magnetic resonance imaging procedures since 1988 and is currently used globally in more than 5 million applications annually. The broadest category of spontaneously reported AEs, subjective symptoms, occurs in less than 0.01% of procedures. Within the total AEs reported, the distribution of serious and nonserious reports was 9.3% and 90.7%, respectively. The rates of AE reporting have changed over time, with increased rates in the second reporting period (1993 to 1997), followed by substantially lower rates in subsequent years. AE reporting rates are the most comprehensive data available; however, there will always be some underestimation of the true event rates. Although no substantial differences were noted among major age groups, substantial differences in reporting frequency were found among regions, with the United States reporting nearly twice as many AEs as Europe in the postmarketing phase. CONCLUSION: The postmarketing utilization and pharmacovigilance analysis of Gd-DTPA has revealed temporal changes and regional differences, overall with an excellent safety profile. Its extensive utilization and safety information have firmly established it as highly used and safe magnetic resonance imaging agent.