Ablation of Locally Advanced Pancreatic Cancer with Percutaneous Irreversible Electroporation: Results of the Phase I/II PANFIRE Study.

Purpose To (a) investigate the safety of percutaneous irreversible electroporation (IRE) for locally advanced pancreatic cancer and (b) evaluate the quality of life (QOL), pain perception, and efficacy in terms of time to local progression, event-free survival, and overall survival (OS). Materials and Methods The study was approved by the local review board (NL42888.029.13). All patients provided written informed consent for study participation, the ablation procedure, and data usage. Between January 2014 and June 2015, 25 patients with histologically proved locally advanced pancreatic cancer 5 cm or smaller (13 women, 12 men; median age, 61 years; age range, 41-78 years) were prospectively included to undergo percutaneous computed tomographic-guided IRE. Patients with a metallic biliary Wallstent, epilepsy, or ventricular arrhythmias were excluded. Kaplan-Meier estimates were used to investigate time to local progression, event-free survival, and OS. Safety was assessed on the basis of adverse events, which were graded according to the Common Terminology Criteria for Adverse Events. Pain perception and QOL were evaluated by using specific questionnaires. Results All patients underwent IRE. The median largest tumor diameter was 4.0 cm (range, 3.3-5.0 cm). After a median follow-up of 12 months (interquartile range: 7-16 months), median event-free survival after IRE was 8 months (95% confidence interval [CI]: 4 months, 12 months); the median time to local progression after IRE was 12 months (95% CI: 8 months, 16 months). The median OS was 11 months from IRE (95% CI: 9 months, 13 months) and 17 months from diagnosis (95% CI: 10 months, 24 months). There were 12 minor complications (grade I or II) and 11 major complications (nine grade III, two grade IV) in 10 patients. There were no deaths within 90 days after IRE. Conclusion Percutaneous IRE for locally advanced pancreatic cancer is generally well tolerated, although major adverse events can occur. Preliminary survival data are encouraging and support the setup of larger phase II and III clinical trials to assess the efficacy of IRE plus chemotherapy in the neoadjuvant and adjuvant or second-line setting compared with more widely adopted regimens such as chemotherapy and/or radiation therapy. © RSNA, 2016 Online supplemental material is available for this article.

MR and CT imaging characteristics and ablation zone volumetry of locally advanced pancreatic cancer treated with irreversible electroporation.

OBJECTIVES: To assess specific imaging characteristics after irreversible electroporation (IRE) for locally advanced pancreatic carcinoma (LAPC) with contrast-enhanced (ce)MRI and ceCT, and to explore the correlation of these characteristics with the development of recurrence. METHODS: Qualitative and quantitative analyses of imaging data were performed on 25 patients treated with percutaneous IRE for LAPC. Imaging characteristics of the ablation zone on ceCT and ceMRI were assessed over a 6-month follow-up period. Contrast ratio scores between pre- and post-treatment were compared. To detect early imaging markers for treatment failure, attenuation characteristics at 6 weeks were linked to the area of recurrence within 6 months. RESULTS: Post-IRE, diffusion-weighted imaging (DWI)-b800 signal intensities decreased in all cases (p < 0.05). Both ceMRI and ceCT revealed absent or decreased contrast enhancement, with a hyperintense rim on ceMRI. Ablation zone volume increase was noted on both modalities in the first 6 weeks, followed by a decrease (p < 0.05). In the patients developing tumour recurrence (5/25), a focal DWI-b800 hyperintense spot at 6 weeks predated unequivocal recurrence on CT. CONCLUSION: The most remarkable signal alterations after pancreatic IRE were shown by DWI-b800 and ceMRI. These early imaging characteristics may be useful to establish technical success and predict treatment outcome. KEY POINTS: • This study describes imaging characteristics after irreversible electroporation (IRE) for pancreatic adenocarcinoma. • Familiarity with typical post-IRE imaging characteristics helps to interpret ablation zones. • Post-IRE, no central and variable rim enhancement are visible on contrast-enhanced imaging. • DWI-b800 may prove useful to predict early tumour recurrence. • Post-IRE examinations reveal an initial volume increase followed by a decrease.

Colorectal liver metastatic disease: efficacy of irreversible electroporation--a single-arm phase II clinical trial (COLDFIRE-2 trial).

BACKGROUND: Irreversible electroporation (IRE) is a novel image-guided tumor ablation technique that has shown promise for the ablation of lesions in proximity to vital structures such as blood vessels and bile ducts. The primary aim of the COLDFIRE-2 trial is to investigate the efficacy of IRE for unresectable, centrally located colorectal liver metastases (CRLM). Secondary outcomes are safety, technical success, and the accuracy of contrast-enhanced (ce)CT and (18)F-FDG PET-CT in the detection of local tumor progression (LTP). METHODS/DESIGN: In this single-arm, multicenter phase II clinical trial, twenty-nine patients with (18)F-FDG PET-avid CRLM ≤ 3,5 cm will be prospectively included to undergo IRE of the respective lesion. All lesions must be unresectable and unsuitable for thermal ablation due to vicinity of vital structures. Technical success is based on ceMRI one day post-IRE. All complications related to the IRE procedure are registered. Follow-up consists of (18)F-FDG PET-CT and 4-phase liver CT at 3-monthly intervals during the first year of follow-up. Treatment efficacy is defined as the percentage of tumors successfully eradicated 12 months after the initial IRE procedure based on clinical follow-up using both imaging modalities, tumor marker and (if available) histopathology. To determine the accuracy of (18)F-FDG PET-CT and ceCT, both imaging modalities will be individually scored by two reviewers that are blinded for the final oncologic outcome. DISCUSSION: To date, patients with a central CRLM unsuitable for resection or thermal ablation have no curative treatment option and are given palliative chemotherapy. For these patients, IRE may prove a life-saving treatment option. The results of the proposed trial may represent an important step towards the implementation of IRE for central liver tumors in the clinical setting. TRIAL REGISTRATION NUMBER: NCT02082782.

Irreversible electroporation for nonthermal tumor ablation in the clinical setting: a systematic review of safety and efficacy.

PURPOSE: To provide an overview of current clinical results of irreversible electroporation (IRE), a novel, nonthermal tumor ablation technique that uses electric pulses to induce cell death, while preserving structural integrity of bile ducts and vessels. METHODS: All in-human literature on IRE reporting safety or efficacy or both was included. All adverse events were recorded. Tumor response on follow-up imaging from 3 months onward was evaluated. RESULTS: In 16 studies, 221 patients had 325 tumors treated in liver (n = 129), pancreas (n = 69), kidney (n = 14), lung (n = 6), lesser pelvis (n = 1), and lymph node (n = 2). No major adverse events during IRE were reported. IRE caused only minor complications in the liver; however, three major complications were reported in the pancreas (bile leak [n = 2], portal vein thrombosis [n = 1]). Complete response at 3 months was 67%-100% for hepatic tumors (93%-100% for tumors o 3 cm). Pancreatic IRE combined with surgery led to prolonged survival compared with control patients (20 mo vs 13 mo) and significant pain reduction. CONCLUSIONS: In cases where other techniques are unsuitable, IRE is a promising modality for the ablation of tumors near bile ducts and blood vessels. This articles gives an extensive overview of the available evidence, which is limited in terms of quality and quantity. With the limitations of the evidence in mind, IRE of central liver tumors seems relatively safe without major complications, whereas complications after pancreatic IRE appear more severe. The available limited results for tumor control are generally good. Overall, the future of IRE for difficult-to-reach tumors appears promising.

Combined non-invasive functional and anatomical diagnostic work-up in clinical practice: the magnetic resonance and computed tomography in suspected coronary artery disease (MARCC) study.

AIMS: The combined use of cardiac computed tomography (CT) coronary angiography (CTCA) and myocardial perfusion imaging allows the non-invasive evaluation of coronary morphology and function. Cardiovascular magnetic resonance (CMR) imaging has several advantages: it can simultaneously assess myocardial perfusion, ventricular and valvular function, cardiomyopathy, and aortic disease and does not involve any additional ionizing radiation. We investigated the combined use of cardiac CT and CMR for the diagnostic evaluation of patients with suspected coronary artery disease (CAD) in clinical practice. METHODS AND RESULTS: A total of 192 patients with low or intermediate pre-test probability of CAD underwent CTCA and CMR. All patients with obstructive CAD on CTCA and/or myocardial ischaemia on CMR were referred for invasive coronary angiography (ICA). Fractional flow reserve was measured in case of intermediate lesions (30-70% diameter stenosis) on ICA. Additional cardiac and extra-cardiac findings by CTCA and CMR were registered. The combination of CTCA and CMR significantly improved specificity and overall accuracy (94 and 91%) for the detection of significant CAD compared with their use as a single technique (CTCA 39 and 57%, P < 0.0001; CMR 82 and 83%, P = 0.016). No events were recorded during follow-up (18 ± 6 months) in 104 patients who did not undergo ICA. Furthermore, the combined strategy provided an alternative diagnosis in 19 patients. CONCLUSION: The combined use of CTCA and CMR significantly improved specificity and overall diagnostic accuracy for the detection of significant CAD and allowed the detection of alternative (extra-)cardiac disease in patients without significant CAD.

Comparison of MR enteroclysis with video capsule endoscopy in the investigation of small-intestinal disease.

PURPOSE: To evaluate the diagnostic accuracy of MR enteroclysis and to compare it to video capsule endoscopy (VCE) in the analysis of suspected small-bowel disease. METHODS: We performed a retrospective analysis of 77 patients who underwent both MR enteroclysis and VCE and compared the findings of these studies with the findings of enteroscopy, surgery, or with the results of clinical follow-up lasting ≥2 years. RESULTS: Findings included malignant neoplasms (n = 13), benign neoplasms (n = 10), refractory celiac disease (n = 4), Crohn's disease (n = 2) and miscellaneous conditions (n = 10). Specificity of MR enteroclysis was higher than that of VCE (0.97 vs. 0.84, P = 0.047), whereas sensitivity was similar (0.79 vs. 0.74, P = 0.591). In 2/32 (6.3%) patients with both negative VCE and negative MR enteroclysis a positive diagnosis was established, compared to 5/11 (45.5%) patients in whom VCE was positive and MR enteroclysis was negative (likelihood ratio 8.1; P = 0.004), 9/11 (81.8%) patients in whom MR enteroclysis was positive and VCE was negative (likelihood ratio 23.5; P < 0.0001), and all 23 patients in whom both VCE and MR enteroclysis showed abnormalities (likelihood ratio 60.8; P < 0.0001). CONCLUSIONS: VCE and MR enteroclysis are complementary modalities. In our study-population, MR enteroclysis was more specific than VCE, while both produced the same sensitivity.

Coronary risk factors and myocardial blood flow in patients evaluated for coronary artery disease: a quantitative [15O]H2O PET/CT study.

BACKGROUND: There has been increasing interest in quantitative myocardial blood flow (MBF) imaging over the last years and it is expected to become a routinely used technique in clinical practice. Positron emission tomography (PET) using [(15)O]H(2)O is the established gold standard for quantification of MBF in vivo. A fundamental issue when performing quantitative MBF imaging is to define the limits of MBF in a clinically suitable population. The aims of the present study were to determine the limits of MBF and to determine the relationship among coronary artery disease (CAD) risk factors, gender and MBF in a predominantly symptomatic patient cohort without significant CAD. METHODS: A total of 128 patients (mean age 54 ± 10 years, 50 men) with a low to intermediate pretest likelihood of CAD were referred for noninvasive evaluation of CAD using a hybrid PET/computed tomography (PET/CT) scanner. MBF was quantified with [(15)O]H(2)O at rest and during adenosine-induced hyperaemia. Obstructive CAD was excluded in these patients by means of invasive or CT-based coronary angiography. RESULTS: Global average baseline MBF values were 0.91 ± 0.34 and 1.09 ± 0.30 ml·min(-1)·g(-1) (range 0.54-2.35 and 0.59-2.75 ml·min(-1)·g(-1)) in men and women, respectively (p < 0.01). However, no gender-dependent difference in baseline MBF was seen following correction for rate-pressure product (0.98 ± 0.45 and 1.09 ± 0.30 ml·min(-1)·g(-1) in men and women, respectively; p = 0.08). Global average hyperaemic MBF values were 3.44 ± 1.20 ml·min(-1)·g(-1) in the whole study population, and 2.90 ± 0.85 and 3.78 ± 1.27 ml·min(-1)·g(-1) (range 1.52-5.22 and 1.72-8.15 ml·min(-1)·g(-1)) in men and women, respectively (p < 0.001). Multivariate analysis identified male gender, age and body mass index as having an independently negative impact on hyperaemic MBF. CONCLUSION: Gender, age and body mass index substantially influence reference values and should be corrected for when interpreting hyperaemic MBF values.

Quantitative relationship between coronary artery calcium score and hyperemic myocardial blood flow as assessed by hybrid 15O-water PET/CT imaging in patients evaluated for coronary artery disease.

BACKGROUND: The incremental value of CAC over traditional risk factors to predict coronary vasodilator dysfunction and inherent myocardial blood flow (MBF) impairment is only scarcely documented (MBF). The aim of this study was therefore to evaluate the relationship between CAC content, hyperemic MBF, and coronary flow reserve (CFR) in patients undergoing hybrid (15)O-water PET/CT imaging. METHODS: We evaluated 173 (mean age 56 ± 10, 78 men) patients with a low to intermediate likelihood for coronary artery disease (CAD), without a documented history of CAD, undergoing vasodilator stress (15)O-water PET/CT and CAC scoring. Obstructive coronary artery disease was excluded by means of invasive (n = 44) or CT-based coronary angiography (n = 129). RESULTS: 91 of 173 patients (52%) had a CAC score of zero. Of those with CAC, the CAC score was 0.1-99.9, 100-399.9, and ≥400 in 31%, 12%, and 5% of patients, respectively. Global CAC score showed significant inverse correlation with hyperemic MBF (r = -0.32, P < .001). With increasing CAC score, there was a decline in hyperemic MBF on a per-patient basis [3.70, 3.30, 2.68, and 2.53 mL · min(-1) · g(-1), with total CAC score of 0, 0.1-99.9, 100-399.9, and ≥400, respectively (P < .001)]. CFR showed a stepwise decline with increasing levels of CAC (3.70, 3.32, 2.94, and 2.93, P < .05). Multivariate analysis, including age, BMI, and CAD risk factors, revealed that only age, male gender, BMI, and hypercholesterolemia were associated with reduced stress perfusion. Furthermore, only diabetes and age were independently associated with CFR. CONCLUSION: In patients without significant obstructive CAD, a greater CAC burden is associated with a decreased hyperemic MBF and CFR. However, this association disappeared after adjustment for traditional CAD risk factors. These results suggest that CAC does not add incremental value regarding hyperemic MBF and CFR over established CAD risk factors in patients without obstructive CAD.

Deep infiltrating endometriosis of the bowel: MR imaging as a method to predict muscular invasion.

PURPOSE: To evaluate magnetic resonance (MR) imaging morphologic- and signal intensity abnormalities of deep infiltrating endometriosis (DIE) of the bowel wall and to assess its value in predicting depth and extent of bowel wall infiltration. MATERIALS AND METHODS: This single-center study was performed in a tertiary referral center for endometriosis. All patients (n = 28) who underwent segmental bowel resection (2004-2010) were retrospectively studied. MR images were analyzed by two experienced readers independently (number of lesions, location, size, signal intensity, and depth of bowel wall infiltration) and this was correlated with histopathology. RESULTS: The sensitivity, specificity, positive and negative predictive values, and accuracy for diagnosis of endometriosis infiltrating the muscular layer of the bowel were 100%, 75%, 96%, 100%, and 96%, respectively. The inter-rater agreement was 0.84. "Fan shaped" configurations with hypointensity on T2- and T1-weighted imaging were characteristic for thickening of indigenous smooth muscle and smooth muscle hyperplasia at histopathology, as a consequence of infiltration by endometriosis. Thickening of the (sub)mucosa corresponded to edema with or without infiltration of endometriosis. CONCLUSION: MR imaging at 1.5 Tesla is useful to predict muscular infiltration of the bowel in endometriosis, whereas it is of limited value in diagnosis of (sub)mucosal infiltration.

MR enteroclysis in refractory celiac disease: proposal and validation of a severity scoring system.

PURPOSE: To determine magnetic resonance (MR) enteroclysis findings in patients with uncomplicated celiac disease (CD), refractory CD (RCD) type I, and RCD type II, to develop and validate a scoring system to identify patients with RCD II and to determine the diagnostic accuracy of MR enteroclysis to detect CD-related malignancies. MATERIALS AND METHODS: This study was performed with approval of the institutional review board. One radiologist blinded to clinical details retrospectively evaluated quantitative and qualitative criteria of 28 studies obtained in symptomatic patients with CD (uncomplicated CD, n = 10; RCD I, n = 8; RCD II, n = 10). A scoring system was developed by using parameters identified in multivariate analysis to be associated with RCD II, which two radiologists evaluated in a second group of 40 symptomatic patients with CD. Accuracy to detect malignancy was assessed in the total study group. Cumulative survival was evaluated in the total study group by using the Kaplan-Meier method. RESULTS: MR enteroclysis could not be used to discriminate between uncomplicated CD and RCD I. The presence of less than 10 folds per 5 cm jejunum, mesenteric fat infiltration, and bowel wall thickening were associated with RCD II. A positive MR score was defined as the presence of two or more of these features. In the validation group, the MR score was positive in 13 of 15 patients with RCD II (sensitivity, 0.87) and negative in 24 of 25 patients without RCD II (specificity, 0.96). The 5-year survival rate was 95% in patients with a negative MR score and 56% in patients with a positive MR score (P < .0001). MR enteroclysis helped to identify the presence of seven of eight malignancies and to diagnose absence of malignancy in 58 of 60 studies. CONCLUSION: MR enteroclysis can be used to investigate the presence of RCD II or malignancy in symptomatic patients with CD.

The Role of 89Zr-Immuno-PET in Navigating and Derisking the Development of Biopharmaceuticals.

The identification of molecular drivers of disease and the compelling rise of biotherapeutics have impacted clinical care but have also come with challenges. Such therapeutics include peptides, monoclonal antibodies, antibody fragments and nontraditional binding scaffolds, activatable antibodies, bispecific antibodies, immunocytokines, antibody-drug conjugates, enzymes, polynucleotides, and therapeutic cells, as well as alternative drug carriers such as nanoparticles. Drug development is expensive, attrition rates are high, and efficacy rates are lower than desired. Almost all these drugs, which in general have a long residence time in the body, can stably be labeled with 89Zr for whole-body PET imaging and quantification. Although not restricted to monoclonal antibodies, this approach is called 89Zr-immuno-PET. This review summarizes the state of the art of the technical aspects of 89Zr-immuno-PET and illustrates why it has potential for steering the design, development, and application of biologic drugs. Appealing showcases are discussed to illustrate what can be learned with this emerging technology during preclinical and especially clinical studies about biologic drug formats and disease targets. In addition, an overview of ongoing and completed clinical trials is provided. Although 89Zr-immuno-PET is a young tool in drug development, its application is rapidly expanding, with first clinical experiences giving insight on why certain drug-target combinations might have better perspectives than others.

MR enteroclysis in the diagnosis of small-bowel neoplasms.

PURPOSE: To evaluate the diagnostic accuracy and interobserver variance of magnetic resonance (MR) enteroclysis in the diagnosis of small-bowel neoplasms, with small-bowel endoscopy, surgery, histopathologic analysis, and follow-up serving as standards of reference, and to identify MR enteroclysis characteristics capable of enabling discrimination between benign and malignant small-bowel neoplasms. MATERIALS AND METHODS: This study was performed in accordance with the guidelines of the institutional review board, and the requirement for informed consent was waived. MR enteroclysis studies of 91 patients (43 women, 48 men; age range, 18-83 years) were retrospectively evaluated by two radiologists blinded to clinical details. Only studies explicitly performed to investigate or exclude the presence of small-bowel neoplasms were included. Radiologic findings were compared with findings of double-balloon endoscopy (n = 45), surgery (n = 18), esophagogastroduodenoscopy (n = 3), ileocolonoscopy (n = 2), autopsy (n = 2), and clinical follow-up for more than 18 months (n = 21). Efficacy parameters were calculated with 95% confidence intervals. Tumor characteristics were compared with the Student t test and the Fisher exact test. RESULTS: Readers 1 and 2 interpreted 31 and 33 studies, respectively, as depicting a small-bowel neoplasm and 19 and 17 studies, respectively, as depicting small-bowel malignancy. In 32 patients, the presence of small-bowel neoplasm was confirmed. In 19 of these patients, the neoplasm was malignant. Sensitivity and specificity in the diagnosis of small-bowel neoplasms was 0.91 and 0.95, respectively, for reader 1 and 0.94 and 0.97, respectively, for reader 2; the kappa value was 0.95. Factors associated with malignancy were the presence of longer solitary nonpedunculated lesions, mesenteric fat infiltration, and enlarged mesenteric lymph nodes. CONCLUSION: Eighty-six of 91 studies were correctly interpreted, resulting in an overall diagnostic accuracy of 0.95 for MR enteroclysis in the detection of small-bowel neoplasms. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090828/-/DC1.

Low to intermediate probability of coronary artery disease: comparison of coronary CT angiography with first-pass MR myocardial perfusion imaging.

PURPOSE: To compare coronary computed tomographic (CT) angiography with first-pass magnetic resonance (MR) myocardial perfusion imaging in patients with chest pain and low to intermediate probability of coronary artery disease (CAD). MATERIALS AND METHODS: Local ethics committee approval and patient written informed consent were obtained. Patients with chest pain and low to intermediate pretest probability of CAD underwent both coronary CT angiography and MR myocardial perfusion imaging. Coronary CT angiographic and MR myocardial perfusion images were analyzed qualitatively by blinded observers. Obstructive CAD was defined as more than 50% diameter stenosis at coronary CT angiography. Data were expressed with 95% confidence intervals (CIs) calculated from binomial expression. RESULTS: In 145 (94.2%) of 154 eligible patients, both coronary CT angiography and MR myocardial perfusion imaging were performed successfully. Mean age was 57 years +/- 10 (standard deviation), and 45.5% of patients were male. Mean interval between coronary CT angiography and MR myocardial perfusion imaging was 4.6 days +/- 3.0; median was 5.0 days. CT coronary angiography revealed obstructive CAD in 52 (35.9%) patients and 78 (17.9%) coronary arteries. At MR myocardial perfusion imaging, myocardial ischemia was demonstrated in 33 (22.8%) patients and 59 (13.6%) vessel territories. Of patients without CAD at coronary CT angiography, 90.5% (57 of 63; 95% CI: 82.6%, 95.0%) had normal myocardial perfusion at MR myocardial perfusion imaging. Of patients with nonobstructive CAD, 83.3% (25 of 30; 95% CI: 69.5%, 91.6%) had normal myocardial perfusion at MR myocardial perfusion imaging. Myocardial ischemia was detected at MR myocardial perfusion imaging in 42.3% (22 of 52; 95% CI: 29.5%, 56%) of patients with obstructive CAD at coronary CT angiography. CONCLUSION: MR myocardial perfusion imaging and coronary CT angiography have complementary roles in evaluation of patients who are suspected of having CAD. Coronary CT angiography can be used to reliably rule out CAD, but its capability to demonstrate hemodynamically significant CAD is limited. The combination of both techniques enables the clinician to evaluate morphology and functional relevance of CAD comprehensively and noninvasively.

Dynamic contrast-enhanced CT in patients treated with sorafenib and erlotinib for non-small cell lung cancer: a new method of monitoring treatment?

OBJECTIVE: We investigated the feasibility of serial dynamic contrast-enhanced computed tomography (DCE-CT) in patients with advanced/metastatic non-small cell lung cancer (NSCLC) receiving anti-angiogenic (sorafenib) and anti-EGFR (erlotinib) treatment, and correlated tumour blood flow (BF) with treatment outcome. METHODS: DCE-CTs were performed at baseline and 3 and 6 weeks after starting treatment. Tumour BF, calculated with the maximum slope method, and percentage change were measured in 23 patients (14 male; median age 59 years). Tumour BF was compared at baseline and weeks 3 and 6; the relation with RECIST/Crabb response and progression-free survival (PFS) was assessed. RESULTS: Mean tumour perfusion decreased from 39.2 ml/100 g/min at baseline to 15.1 ml/100 g/min at week 3 (p < 0.001) and 9.4 ml/100 g/min at week 6 (p < 0.001). Tumour perfusion was lower in RECIST and Crabb responders versus non-responders at week 3 (4.2 versus 17.7 ml/100 g/min, p = 0.03) and week 6 (0 versus 13.4 ml/100 g/min, p = 0.04). Patients with a decrease larger than the median at week 6 tended to have a longer PFS (7.1 versus 5.7 months, p = 0.06). CONCLUSION: Serial DCE-CTs are feasible in patients with NSCLC and demonstrated a significant decrease in tumour BF following sorafenib/erlotinib therapy. Early changes in tumour BF correlated with objective response and showed a trend towards longer PFS.

Criteria for the selective use of chest computed tomography in blunt trauma patients.

PURPOSE: The purpose of this study was to derive parameters that predict which high-energy blunt trauma patients should undergo computed tomography (CT) for detection of chest injury. METHODS: This observational study prospectively included consecutive patients (>or=16 years old) who underwent multidetector CT of the chest after a high-energy mechanism of blunt trauma in one trauma centre. RESULTS: We included 1,047 patients (median age, 37; 70% male), of whom 508 had chest injuries identified by CT. Using logistic regression, we identified nine predictors of chest injury presence on CT (age >or=55 years, abnormal chest physical examination, altered sensorium, abnormal thoracic spine physical examination, abnormal chest conventional radiography (CR), abnormal thoracic spine CR, abnormal pelvic CR or abdominal ultrasound, base excess <-3 mmol/l and haemoglobin <6 mmol/l). Of 855 patients with >or=1 positive predictors, 484 had injury on CT (95% of all 508 patients with injury). Of all 192 patients with no positive predictor, 24 (13%) had chest injury, of whom 4 (2%) had injuries that were considered clinically relevant. CONCLUSION: Omission of CT in patients without any positive predictor could reduce imaging frequency by 18%, while most clinically relevant chest injuries remain adequately detected.

Incremental prognostic value of hybrid [15O]H2O positron emission tomography-computed tomography: combining myocardial blood flow, coronary stenosis severity, and high-risk plaque morphology.

AIMS: This study sought to determine the prognostic value of combined functional testing using positron emission tomography (PET) perfusion imaging and anatomical testing using coronary computed tomography angiography (CCTA)-derived stenosis severity and plaque morphology in patients with suspected coronary artery disease (CAD). METHODS AND RESULTS: In this retrospective study, 539 patients referred for hybrid [15O]H2O PET-CT imaging because of suspected CAD were investigated. PET was used to determine myocardial blood flow (MBF), whereas CCTA images were evaluated for obstructive stenoses and high-risk plaque (HRP) morphology. Patients were followed up for the occurrence of all-cause death and non-fatal myocardial infarction (MI). During a median follow-up of 6.8 (interquartile range 4.8-7.8) years, 42 (7.8%) patients experienced events, including 23 (4.3%) deaths, and 19 (3.5%) MIs. Annualized event rates for normal vs. abnormal results of PET MBF, CCTA-derived stenosis, and HRP morphology were 0.6 vs. 2.1%, 0.4 vs. 2.1%, and 0.8 vs. 2.8%, respectively (P < 0.001 for all). Cox regression analysis demonstrated prognostic values of PET perfusion imaging [hazard ratio (HR) 3.75 (1.84-7.63), P < 0.001], CCTA-derived stenosis [HR 5.61 (2.36-13.34), P < 0.001], and HRPs [HR 3.37 (1.83-6.18), P < 0.001] for the occurrence of death or MI. However, only stenosis severity [HR 3.01 (1.06-8.54), P = 0.039] and HRPs [HR 1.93 (1.00-3.71), P = 0.049] remained independently associated. CONCLUSION: PET-derived MBF, CCTA-derived stenosis severity, and HRP morphology were univariably associated with death and MI, whereas only stenosis severity and HRP morphology provided independent prognostic value.

Predictive value of targeted proteomics for coronary plaque morphology in patients with suspected coronary artery disease.

BACKGROUND: Risk stratification is crucial to improve tailored therapy in patients with suspected coronary artery disease (CAD). This study investigated the ability of targeted proteomics to predict presence of high-risk plaque or absence of coronary atherosclerosis in patients with suspected CAD, defined by coronary computed tomography angiography (CCTA). METHODS: Patients with suspected CAD (n = 203) underwent CCTA. Plasma levels of 358 proteins were used to generate machine learning models for the presence of CCTA-defined high-risk plaques or complete absence of coronary atherosclerosis. Performance was tested against a clinical model containing generally available clinical characteristics and conventional biomarkers. FINDINGS: A total of 196 patients with analyzable protein levels (n = 332) was included for analysis. A subset of 35 proteins was identified predicting the presence of high-risk plaques. The developed machine learning model had fair diagnostic performance with an area under the curve (AUC) of 0·79 ±â€¯0·01, outperforming prediction with generally available clinical characteristics (AUC = 0·65 ±â€¯0·04, p < 0·05). Conversely, a different subset of 34 proteins was predictive for the absence of CAD (AUC = 0·85 ±â€¯0·05), again outperforming prediction with generally available characteristics (AUC = 0·70 ±â€¯0·04, p < 0·05). INTERPRETATION: Using machine learning models, trained on targeted proteomics, we defined two complementary protein signatures: one for identification of patients with high-risk plaques and one for identification of patients with absence of CAD. Both biomarker subsets were superior to generally available clinical characteristics and conventional biomarkers in predicting presence of high-risk plaque or absence of coronary atherosclerosis. These promising findings warrant external validation of the value of targeted proteomics to identify cardiovascular risk in outcome studies. FUND: This study was supported by an unrestricted research grant from HeartFlow Inc. and partly supported by a European Research Area Network on Cardiovascular Diseases (ERA-CVD) grant (ERA CVD JTC2017, OPERATION). Funders had no influence on trial design, data evaluation, and interpretation.

Diagnostic Value of Transluminal Attenuation Gradient for the Presence of Ischemia as Defined by Fractional Flow Reserve and Quantitative Positron Emission Tomography.

OBJECTIVES: The aim of this study was to investigate the incremental diagnostic value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (TAG-CCO), and transluminal diameter gradient (TDG) over coronary computed tomography angiography (CTA)-derived diameter stenosis alone for the identification of ischemia as defined by both the invasive reference standard fractional flow reserve (FFR) and the noninvasive reference standard quantitative positron emission tomography (PET). BACKGROUND: In addition to anatomic information obtained by coronary CTA, several functional CT parameters have been proposed to identify hemodynamically significant lesions more accurately, such as TAG, TAG-CCO, and more recently TDG. However, clinical validation studies have reported conflicting results, and a recent study has suggested that TAG may be affected by changes in vessel diameter. METHODS: Patients with suspected coronary artery disease underwent coronary CTA and [15O]H2O PET followed by invasive coronary angiography with FFR of all major coronary arteries. TAG, TAG-CCO, and TDG were assessed, and the incremental diagnostic value of these parameters over coronary CTA-derived diameter stenosis alone for ischemia as defined by PET (hyperemic myocardial blood flow ≤2.30 ml/min/g) and FFR (≤0.80) was determined. RESULTS: A total of 557 (91.9%) coronary arteries of 201 patients were included for analysis. TAG, TAG-CCO, and TDG did not discriminate between vessels with or without ischemia as defined by either PET or FFR. Furthermore, these parameters did not have incremental diagnostic accuracy over coronary CTA alone for the presence of ischemia as defined by PET and FFR. There was a significant correlation between TDG and TAG (r = 0.47; p < 0.001) and between TDG and TAG-CCO (r = 0.37; p < 0.001). CONCLUSIONS: TAG, TAG-CCO, and TDG do not provide incremental diagnostic value over coronary CTA alone for the presence of ischemia as defined by [15O]H2O PET and/or FFR. The lack of diagnostic value of contrast enhancement-based flow estimations appears related to coronary luminal dimension variability.

Arm raising at exposure-controlled multidetector trauma CT of thoracoabdominal region: higher image quality, lower radiation dose.

PURPOSE: To evaluate the effect of arm position on image quality and effective radiation dose in an automatic exposure-controlled (AEC) multidetector thoracoabdominal computed tomography (CT) protocol in trauma patients. MATERIALS AND METHODS: This retrospective study of the data of 177 trauma patients (117 male; median age, 39 years) was approved by the institutional ethics board, with informed patient consent waived. Patients underwent scanning by using an AEC 16-detector thoracoabdominal CT protocol in which both arms were raised above the shoulder region (standard-position group, 132 patients), one arm was raised and the other was down (one-arm group, 27 patients), or both arms were down (two-arm group, 18 patients). Objective and subjective image quality was assessed. Individual effective radiation dose was calculated from the effective tube current-time product per exposed section. For this purpose, section location-dependent conversion factors were derived by using a CT dosimetry calculator. The effect of arm position on effective dose was quantified by using linear regression analysis with correction for patient volume and attenuation. RESULTS: Compared with the image quality in the standard-position group, the image quality in the one- and two-arm groups was decreased but within acceptable diagnostic limits. The median corrected effective dose in the standard-position group was 18.6 mSv; the dose in the one-arm group was 18% (95% confidence interval: 11%, 25%) higher than this, and that in the two-arm group was 45% (95% confidence interval: 34%, 57%) higher. CONCLUSION: Omitting arm raising results in lower but acceptable image quality and a substantially higher effective radiation dose. Hence, effort should be made to position the arms above the shoulder when scanning trauma patients. Clinical trial registration no. NCT00228111.

Comparison of Coronary CT Angiography, SPECT, PET, and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve.

Importance: At present, the choice of noninvasive testing for a diagnosis of significant coronary artery disease (CAD) is ambiguous, but nuclear myocardial perfusion imaging with single-photon emission tomography (SPECT) or positron emission tomography (PET) and coronary computed tomography angiography (CCTA) is predominantly used for this purpose. However, to date, prospective head-to-head studies are lacking regarding the diagnostic accuracy of these imaging modalities. Furthermore, the combination of anatomical and functional assessments configuring a hybrid approach may yield improved accuracy. Objectives: To establish the diagnostic accuracy of CCTA, SPECT, and PET and explore the incremental value of hybrid imaging compared with fractional flow reserve. Design, Setting, and Participants: A prospective clinical study involving 208 patients with suspected CAD who underwent CCTA, technetium 99m/tetrofosmin-labeled SPECT, and [15O]H2O PET with examination of all coronary arteries by fractional flow reserve was performed from January 23, 2012, to October 25, 2014. Scans were interpreted by core laboratories on an intention-to-diagnose basis. Hybrid images were generated in case of abnormal noninvasive anatomical or functional test results. Main Outcomes and Measures: Hemodynamically significant stenosis in at least 1 coronary artery as indicated by a fractional flow reserve of 0.80 or less and relative diagnostic accuracy of SPECT, PET, and CCTA in detecting hemodynamically significant CAD. Results: Of the 208 patients in the study (76 women and 132 men; mean [SD] age, 58 [9] years), 92 (44.2%) had significant CAD (fractional flow reserve ≤0.80). Sensitivity was 90% (95% CI, 82%-95%) for CCTA, 57% (95% CI, 46%-67%) for SPECT, and 87% (95% CI, 78%-93%) for PET, whereas specificity was 60% (95% CI, 51%-69%) for CCTA, 94% (95% CI, 88%-98%) for SPECT, and 84% (95% CI, 75%-89%) for PET. Single-photon emission tomography was found to be noninferior to PET in terms of specificity (P < .001) but not in terms of sensitivity (P > .99) using the predefined absolute margin of 10%. Diagnostic accuracy was highest for PET (85%; 95% CI, 80%-90%) compared with that of CCTA (74%; 95% CI, 67%-79%; P = .003) and SPECT (77%; 95% CI, 71%-83%; P = .02). Diagnostic accuracy was not enhanced by either hybrid SPECT and CCTA (76%; 95% CI, 70%-82%; P = .75) or by PET and CCTA (84%; 95% CI, 79%-89%; P = .82), but resulted in an increase in specificity (P = .004) at the cost of a decrease in sensitivity (P = .001). Conclusions and Relevance: This controlled clinical head-to-head comparative study revealed PET to exhibit the highest accuracy for diagnosis of myocardial ischemia. Furthermore, a combined anatomical and functional assessment does not add incremental diagnostic value but guides clinical decision-making in an unsalutary fashion.