Use of 18F-fluorodeoxyglucose positron emission tomography to standardize clinical trial recruitment in Takayasu's arteritis.

OBJECTIVES: To assess whether data from 18F-fluorodeoxyglucose (FDG) PET should be incorporated into eligibility criteria for clinical trials in Takayasu's arteritis (TAK). METHODS: The study was conducted in two parts. Part one was an international online survey among physicians with experience managing TAK to determine, using clinical vignettes, whether FDG-PET data influence decisions about enrolment in trials. Part two used patient data from an observational cohort study in TAK to assess agreement regarding decisions about enrolment into trials, based on clinical assessment with and without incorporation of FDG-PET data. RESULTS: In part one, 68 physicians responded to the survey. Most physicians had used FDG-PET to diagnose TAK (82%) or monitor disease activity (66%). In vignettes representing active clinical disease, FDG-PET findings increased physician confidence in disease assessment and reduced outlier assessments. The greatest variability in decisions regarding enrolment into trials was observed in vignettes representing constitutional symptoms alone and elevated acute-phase reactants. In these cases, FDG-PET findings influenced decisions about enrolment and improved physician confidence. In multivariable models, FDG-PET findings were 1.29 times more strongly associated with enrolment decisions compared with levels of acute-phase reactants. In part two, incorporation of FDG-PET data significantly improved agreement about enrolment decisions between raters [inter-rater reliability (IRR) = 0.68 (95% CI 0.67, 0.69) to IRR = 0.88 (95% CI 0.87, 0.89); P < 0.01]. CONCLUSIONS: Incorporation of FDG-PET data into assessment of TAK influences decisions about enrolment of patients into trials, improves physician confidence about clinical assessment and could help reduce variability in study populations. Future trials in TAK should consider incorporating FDG-PET data into eligibility criteria.

Use of 18F-fluorodeoxyglucose positron emission tomography to monitor tocilizumab effect on vascular inflammation in giant cell arteritis.

OBJECTIVES: To evaluate the time-dependent effects of tocilizumab on vascular inflammation as measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in GCA. METHODS: Patients with GCA treated with tocilizumab were selected from a prospective, observational cohort. Patients underwent FDG-PET at the baseline visit prior to initiation of tocilizumab and at subsequent follow-up visits performed at 6-month intervals. All imaging findings were interpreted blinded to clinical data. The PET vascular activity score (PETVAS) was used to quantify arterial FDG uptake. Wilcoxon signed rank test was used to compare change in PETVAS between visits. Linear regression was used to determine change in PETVAS over multiple timepoints. RESULTS: Twenty-five patients with GCA were included. All patients had physician-determined active vasculitis at the baseline visit by clinical assessment and FDG-PET interpretation. PETVAS was significantly reduced in association with tocilizumab treatment from the baseline to the most recent follow-up visit [24.0 (IQR 22.3-27.0) vs 18.5 (IQR 15.3-23.8); P <0.01]. A significant reduction in PETVAS was observed over a two-year treatment period (P <0.01 for linear trend), with a similar degree of improvement in both the first and second years of treatment. Repeat FDG-PET scans after tocilizumab discontinuation showed worsening PET activity in five out of six patients, with two patients subsequently experiencing clinical relapse. CONCLUSION: Treatment of patients with GCA with tocilizumab was associated with both clinical improvement and reduction of vascular inflammation as measured by serial FDG-PET. Future clinical trials in GCA should study direct treatment effect on vascular inflammation as an outcome measure.

Clinical symptoms and associated vascular imaging findings in Takayasu's arteritis compared to giant cell arteritis.

OBJECTIVE: To compare the presence of head, neck and upper extremity symptoms in patients with Takayasu's (TAK) and giant cell arteritis (GCA) and their association with vascular inflammation assessed by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) or arterial damage assessed by magnetic resonance angiography (MRA). METHODS: Patients with TAK and GCA underwent clinical and imaging assessments within 24 hours, blinded to each other. Vascular inflammation was defined as arterial FDG-PET uptake greater than liver by visual assessment. Arterial damage was defined as stenosis, occlusion, or aneurysm by MRA. Clinically reported symptoms were compared with corresponding imaging findings using generalised mixed model regression. Cranial symptoms were studied in association with burden of arterial disease in the neck using ordinal regression. RESULTS: Participants with TAK (n=56) and GCA (n=54) contributed data from 270 visits. Carotidynia was reported only in patients with TAK (21%) and was associated with vascular inflammation (p<0.01) but not damage (p=0.33) in the corresponding carotid artery. Posterior headache was reported in TAK (16%) and GCA (20%) but was only associated with corresponding vertebral artery inflammation and damage in GCA (p<0.01). Arm claudication was associated with subclavian artery damage (p<0.01) and inflammation (p=0.04) in TAK and with damage in GCA (p<0.01). Patients with an increased burden of damaged neck arteries were more likely to experience positional lightheadedness (p<0.01) or a major central nervous system event (p=0.01). CONCLUSION: The distribution of symptoms and association with imaging abnormalities differs in patients with TAK and GCA. These findings may help clinicians predict associated FDG-PET and MRA findings based on a specific clinical symptom. CLINICAL TRIAL REGISTRATION NUMBER: NCT02257866.

Association of aortic vascular uptake of 18FDG by PET/CT and aortic wall thickness by MRI in psoriasis: a prospective observational study.

BACKGROUND: The contribution of inflammation to the incidence of cardiovascular disease (CVD) has been increasingly recognized in recent years. We investigated the relationship of aortic vascular uptake of 18F-FDG by PET/CT and aortic wall thickness (AWT) by MRI in psoriasis, a chronic inflammatory disease with increased incidence of CVD. One hundred sixty-five patients with plaque psoriasis participated in an ongoing longitudinal cohort study. Subclinical atherosclerosis was assessed as aortic uptake of 18F-FDG by PET/CT reported as target-to-background ratio (TBR) and AWT by MRI reported as maximal thickness. RESULTS: Patients with psoriasis were middle aged, predominantly male, and had mild CV risk by traditional risk factors. Psoriasis severity as measured by PASI score was a notable determinant of AWT (ρ = 0.20, p = 0.01). Moreover, aortic vascular uptake of 18F-FDG associated with AWT by MRI at baseline in unadjusted analysis (ß = 0.27 p = 0.001) and following adjustment for traditional cardiovascular risk factors, waist-to-hip ratio, and statin use (ß = 0.21 p = 0.01). Finally, following 1 year of psoriasis treatment, a decrease in aortic vascular uptake of 18F-FDG was associated with a reduction in AWT in fully adjusted models (ß = 0.33, p = 0.02). CONCLUSION: In conclusion, we demonstrate that psoriasis severity and aortic vascular uptake of 18F-FDG in the aorta were associated with AWT. Following treatment of psoriasis, a decrease in aortic vascular uptake of 18F-FDG was associated with a reduction in AWT at 1 year. These findings suggest that aortic vascular uptake of 18F-FDG is associated with early evidence of vascular disease assessed by aortic wall thickness. Prospective studies in larger populations including other inflammatory diseases are warranted.

Comparison of magnetic resonance angiography and 18F-fluorodeoxyglucose positron emission tomography in large-vessel vasculitis.

OBJECTIVES: To assess agreement between interpretation of magnetic resonance angiography (MRA) and 18F-fluorodeoxyglucose positron emission tomography (PET) for disease extent and disease activity in large-vessel vasculitis (LVV) and determine associations between imaging and clinical assessments. METHODS: Patients with giant cell arteritis (GCA), Takayasu's arteritis (TAK) and comparators were recruited into a prospective, observational cohort. Imaging and clinical assessments were performed concurrently, blinded to each other. Agreement was assessed by per cent agreement, Cohen's kappa and McNemar's test. Multivariable logistic regression identified MRA features associated with PET scan activity. RESULTS: Eighty-four patients (GCA=35; TAK=30; comparator=19) contributed 133 paired studies. Agreement for disease extent between MRA and PET was 580 out of 966 (60%) arterial territories with Cohen's kappa=0.22. Of 386 territories with disagreement, MRA demonstrated disease in more territories than PET (304vs82, p<0.01). Agreement for disease activity between MRA and PET was 90 studies (68%) with Cohen's kappa=0.30. In studies with disagreement, MRA demonstrated activity in 23 studies and PET in 20 studies (p=0.76). Oedema and wall thickness on MRA were independently associated with PET scan activity. Clinical status was associated with disease activity by PET (p<0.01) but not MRA (p=0.70), yet 35/69 (51%) patients with LVV in clinical remission had active disease by both MRA and PET. CONCLUSIONS: In assessment of LVV, MRA and PET contribute unique and complementary information. MRA better captures disease extent, and PET scan is better suited to assess vascular activity. Clinical and imaging-based assessments often do not correlate over the disease course in LVV. TRIAL REGISTRATION NUMBER: NCT02257866.

End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted EPOCH-R: a paradigm shift in clinical decision making.

Dose-adjusted-EPOCH-R obviates the need for radiotherapy in most patients with primary mediastinal B-cell lymphoma. End-of-treatment PET, however, does not accurately identify patients at risk of treatment failure, thereby confounding clinical decision making. To define the role of PET in primary mediastinal B-cell lymphoma following dose-adjusted-EPOCH-R, we extended enrollment and follow up on our published phase II trial and independent series. Ninety-three patients received dose-adjusted-EPOCH-R without radiotherapy. End-of-treatment PET was performed in 80 patients, of whom 57 received 144 serial scans. One nuclear medicine physician from each institution blindly reviewed all scans from their respective institution. End-of-treatment PET was negative (Deauville 1-3) in 55 (69%) patients with one treatment failure (8-year event-free and overall survival of 96.0% and 97.7%). Among 25 (31%) patients with a positive (Deauville 4-5) end-of-treatment PET, there were 5 (20%) treatment failures (8-year event-free and overall survival of 71.1% and 84.3%). Linear regression analysis of serial scans showed a significant decrease in SUVmax in positive end-of-treatment PET non-progressors compared to an increase in treatment failures. Among 6 treatment failures, the median end-of-treatment SUVmax was 15.4 (range, 1.9-21.3), and 4 achieved long-term remission with salvage therapy. Virtually all patients with a negative end-of-treatment PET following dose-adjusted-EPOCH-R achieved durable remissions and should not receive radiotherapy. Among patients with a positive end-of-treatment PET, only 5/25 (20%) had treatment-failure. Serial PET imaging distinguished end-of-treatment PET positive patients without treatment failure, thereby reducing unnecessary radiotherapy by 80%, and should be considered in all patients with an initial positive PET following dose-adjusted-EPOCH-R (clinicaltrials.gov identifier 00001337).

GlycA Is a Novel Biomarker of Inflammation and Subclinical Cardiovascular Disease in Psoriasis.

RATIONALE: GlycA, an emerging inflammatory biomarker, predicted cardiovascular events in population-based studies. Psoriasis, an inflammatory disease associated with increased cardiovascular risk, provides a model to study inflammatory biomarkers in cardiovascular disease (CVD). Whether GlycA associates with psoriasis and how it predicts subclinical CVD beyond high-sensitivity C-reactive protein in psoriasis is unknown. OBJECTIVE: To investigate the relationships between GlycA and psoriasis and between GlycA and subclinical CVD. METHODS AND RESULTS: Patients with psoriasis and controls (n=412) participated in a 2-stage study. We measured GlycA by nuclear magnetic resonance spectroscopy. National Institutes of Health (NIH) participants underwent 18-F Fluorodeoxyglucose Positron Emission Tomography Computed Tomography (18-FDG PET/CT) scans to assess vascular inflammation (VI) and coronary computed tomographic angiography to quantify coronary artery disease burden. Psoriasis cohorts were young (mean age=47.9), with low cardiovascular risk and moderate skin disease. high-sensitivity C-reactive protein and GlycA were increased in psoriasis compared with controls (GlycA: [PENN: 408.8±75.4 versus 289.4±60.2, P<0.0001; NIH: 415.8±63.2 versus 346.2±46, P<0.0001]) and demonstrated a dose-response with psoriasis severity. In stage 2, VI (ß=0.36, P<0.001) and coronary artery disease (ß=0.29, P=0.004) associated with GlycA beyond CV risk factors in psoriasis. In receiver operating characteristic analysis, GlycA added value in predicting VI (P=0.01) and coronary artery disease (P<0.01). Finally, initiating anti-tumor necrosis factor therapy (n=16) reduced psoriasis severity (P<0.001), GlycA (463.7±92.5 versus 370.1±78.5, P<0.001) and VI (1.93±0.36 versus 1.76±0.19, P<0.001), whereas GlycA remained associated with VI (ß=0.56, P<0.001) post treatment. CONCLUSIONS: GlycA associated with psoriasis severity and subclinical CVD beyond traditional CV risk and high-sensitivity C-reactive protein. Moreover, psoriasis treatment reduced GlycA and VI. These findings support the potential use of GlycA in subclinical CVD risk assessment in psoriasis and potentially other inflammatory diseases.

Feasibility of Dose-reduced Chest CT with Photon-counting Detectors: Initial Results in Humans.

Purpose To investigate whether photon-counting detector (PCD) technology can improve dose-reduced chest computed tomography (CT) image quality compared with that attained with conventional energy-integrating detector (EID) technology in vivo. Materials and Methods This was a HIPAA-compliant institutional review board-approved study, with informed consent from patients. Dose-reduced spiral unenhanced lung EID and PCD CT examinations were performed in 30 asymptomatic volunteers in accordance with manufacturer-recommended guidelines for CT lung cancer screening (120-kVp tube voltage, 20-mAs reference tube current-time product for both detectors). Quantitative analysis of images included measurement of mean attenuation, noise power spectrum (NPS), and lung nodule contrast-to-noise ratio (CNR). Images were qualitatively analyzed by three radiologists blinded to detector type. Reproducibility was assessed with the intraclass correlation coefficient (ICC). McNemar, paired t, and Wilcoxon signed-rank tests were used to compare image quality. Results Thirty study subjects were evaluated (mean age, 55.0 years ± 8.7 [standard deviation]; 14 men). Of these patients, 10 had a normal body mass index (BMI) (BMI range, 18.5-24.9 kg/m2; group 1), 10 were overweight (BMI range, 25.0-29.9 kg/m2; group 2), and 10 were obese (BMI ≥30.0 kg/m2, group 3). PCD diagnostic quality was higher than EID diagnostic quality (P = .016, P = .016, and P = .013 for readers 1, 2, and 3, respectively), with significantly better NPS and image quality scores for lung, soft tissue, and bone and with fewer beam-hardening artifacts (all P < .001). Image noise was significantly lower for PCD images in all BMI groups (P < .001 for groups 1 and 3, P < .01 for group 2), with higher CNR for lung nodule detection (12.1 ± 1.7 vs 10.0 ± 1.8, P < .001). Inter- and intrareader reproducibility were good (all ICC > 0.800). Conclusion Initial human experience with dose-reduced PCD chest CT demonstrated lower image noise compared with conventional EID CT, with better diagnostic quality and lung nodule CNR. © RSNA, 2017 Online supplemental material is available for this article.

The relationship between duration of psoriasis, vascular inflammation, and cardiovascular events.

BACKGROUND: Psoriasis is associated with risk of cardiovascular (CV) disease (CVD) and a major adverse CV event (MACE). Whether psoriasis duration affects risk of vascular inflammation and MACEs has not been well characterized. OBJECTIVES: We utilized two resources to understand the effect of psoriasis duration on vascular disease and CV events: (1) a human imaging study and (2) a population-based study of CVD events. METHODS: First, patients with psoriasis (N = 190) underwent fludeoxyglucose F 18 positron emission tomography/computed tomography (duration effect reported as a ß-coefficient). Second, MACE risk was examined by using nationwide registries (adjusted hazard ratios in patients with psoriasis (n = 87,161) versus the general population (n = 4,234,793). RESULTS: In the human imaging study, patients were young, of low CV risk by traditional risk scores, and had a high prevalence of cardiometabolic diseases. Vascular inflammation by fludeoxyglucose F 18 positron emission tomography/computed tomography was significantly associated with disease duration (ß = 0.171, P = .002). In the population-based study, psoriasis duration had strong relationship with MACE risk (1.0% per additional year of psoriasis duration [hazard ratio, 1.010; 95% confidence interval, 1.007-1.013]). LIMITATIONS: These studies utilized observational data. CONCLUSION: We found detrimental effects of psoriasis duration on vascular inflammation and MACE, suggesting that cumulative duration of exposure to low-grade chronic inflammation may accelerate vascular disease development and MACEs. Providers should consider inquiring about duration of disease to counsel for heightened CVD risk in psoriasis.

Cardiac Applications of PET-MR.

PURPOSE OF REVIEW: The purpose of this study was to provide an overview of the clinical applications of PET-MR in the setting of cardiac imaging with emphasis on specific scenarios where both techniques together provided added information. RECENT FINDINGS: Synergy of cardiac PET and MR fusion may hold similar promise eliminating ionizing radiation and improving tissue contrast. Future development of new hybrid scanners, use of new imaging tracers, and clinical applications are significant factors which will influence its use. Both positron emission tomography (PET) and cardiac magnetic resonance imaging (CMR) provide important anatomic and physiologic information with regard to the heart. Being able to combine the data from these two examinations in a hybrid technique allows for a more complete evaluation of cardiac pathology. While hybrid PET-CT has already established the utility of a combined imaging approach, the use of CMR in lieu of CT allows for elimination of ionizing radiation and for improved tissue contrast.

Coronary CT Angiography: Variability of CT Scanners and Readers in Measurement of Plaque Volume.

Purpose To determine reader and computed tomography (CT) scan variability for measurement of coronary plaque volume. Materials and Methods This HIPAA-compliant study followed Standards for Reporting of Diagnostic Accuracy guidelines. Baseline coronary CT angiography was performed in 40 prospectively enrolled subjects (mean age, 67 years ± 6 [standard deviation]) with asymptomatic hyperlipidemia by using a 320-detector row scanner (Aquilion One Vision; Toshiba, Otawara, Japan). Twenty of these subjects underwent coronary CT angiography repeated on a separate day with the same CT scanner (Toshiba, group 1); 20 subjects underwent repeat CT performed with a different CT scanner (Somatom Force; Siemens, Forchheim, Germany [group 2]). Intraclass correlation coefficients (ICCs) and Bland-Altman analysis were used to assess interreader, intrareader, and interstudy reproducibility. Results Baseline and repeat coronary CT angiography scans were acquired within 19 days ± 6. Interreader and intrareader agreement rates were high for total, calcified, and noncalcified plaques for both CT scanners (all ICCs ≥ 0.96) without bias. Scanner variability was ±18.4% (coefficient of variation) with same-vendor follow-up. However, scanner variability increased to ±29.9% with different-vendor follow-up. The sample size to detect a 5% change in noncalcified plaque volume with 90% power and an α error of .05 was 286 subjects for same-CT scanner follow-up and 753 subjects with different-vendor follow-up. Conclusion State-of-the-art coronary CT angiography with same-vendor follow-up has good scan-rescan reproducibility, suggesting a role of coronary CT angiography in monitoring coronary artery plaque response to therapy. Differences between coronary CT angiography vendors resulted in lower scan-rescan reproducibility. © RSNA, 2016 Online supplemental material is available for this article.

Severity of Psoriasis Associates With Aortic Vascular Inflammation Detected by FDG PET/CT and Neutrophil Activation in a Prospective Observational Study.

OBJECTIVE: To understand whether directly measured psoriasis severity is associated with vascular inflammation assessed by (18)F-fluorodeoxyglucose positron emission tomography computed tomography. APPROACH: In-depth cardiovascular and metabolic phenotyping was performed in adult psoriasis patients (n=60) and controls (n=20). Psoriasis severity was measured using psoriasis area severity index. Vascular inflammation was measured using average aortic target-to-background ratio using (18)F-fluorodeoxyglucose positron emission tomography computed tomography. RESULTS: Both the psoriasis patients (28 men and 32 women, mean age 47 years) and controls (13 men and 7 women, mean age 41 years) were young with low cardiovascular risk. Psoriasis area severity index scores (median 5.4; interquartile range 2.8-8.3) were consistent with mild-to-moderate skin disease severity. Increasing psoriasis area severity index score was associated with an increase in aortic target-to-background ratio (ß=0.41, P=0.001), an association that changed little after adjustment for age, sex, and Framingham risk score. We observed evidence of increased neutrophil frequency (mean psoriasis, 3.7±1.2 versus 2.9±1.2; P=0.02) and activation by lower neutrophil surface CD16 and CD62L in blood. Serum levels of S100A8/A9 (745.1±53.3 versus 195.4±157.8 ng/mL; P<0.01) and neutrophil elastase-1 (43.0±2.4 versus 30.8±6.7 ng/mL; P<0.001) were elevated in psoriasis. Finally, S100A8/A9 protein was related to both psoriasis skin disease severity (ß=0.53; P=0.02) and vascular inflammation (ß=0.48; P=0.02). CONCLUSIONS: Psoriasis severity is associated with vascular inflammation beyond cardiovascular risk factors. Psoriasis increased neutrophil activation and neutrophil markers, and S100A8/A9 was related to both skin disease severity and vascular inflammation.

Part 2 - Coronary angiography with gadofosveset trisodium: a prospective intra-subject comparison for dose optimization for 100 % efficiency imaging.

BACKGROUND: Three tesla (3T) coronary magnetic resonance angiography (MRA) may be optimized using gadolinium-based contrast agents (GBCA) such as gadofosveset trisodium. The goal of this study was to evaluate if there is a qualitative or quantitative improvement in the coronary arteries with variation in contrast dose. METHODS: Twenty-eight healthy volunteers were prospectively recruited for coronary MRA at 3T using a steady state injection technique for 3D radial whole-heart image acquisition with retrospective respiratory self-gating (ClinicalTrials.gov identifier: NCT01853592). Nineteen volunteers completed both single- and double-dose imaging instances (0.03 and 0.06 mmol/kg, respectively). Intra-individual comparison of image quality was assessed by measurement of apparent signal/contrast-to-noise ratio (aSNR/aCNR) and subjective evaluation of image quality by 2 independent reviewers. RESULTS: The average duration of coronary MRA acquisition was 7.2 ± 1.2 min. There was significantly higher (60 %, p < 0.001) aSNR of the aorta and right/left ventricle for the double dose compared to single dose injection scheme and aSNR of the coronary arteries increased by 70 % (p < 0.001) for the double dose injection. aCNR increased by +55 % and +60 % in the ventricles and coronary arteries, respectively (p < 0.001). Overall segmental artery visualization for single dose was possible 47 % of the time, which improved to 60 % with double dose (p = 0.019), predominantly driven by improvements in more distal segment visualization (+40 % improvement in mid arterial segments, p = 0.013). CONCLUSIONS: Gadofosveset trisodium dose of 0.06 mmol/kg significantly quantitatively and qualitatively improves the coronary artery image quality compared to 0.03 mmol/kg at 3T for moderate duration (6-8 min) steady state contrast enhanced coronary MRA.

Coronary Plaque Burden at Coronary CT Angiography in Asymptomatic Men and Women.

Purpose To assess the relationship between total, calcified, and noncalcified coronary plaque burdens throughout the entire coronary vasculature at coronary computed tomographic (CT) angiography in relationship to cardiovascular risk factors in asymptomatic individuals with low-to-moderate risk. Materials and Methods This HIPAA-compliant study had institutional review board approval, and written informed consent was obtained. Two hundred two subjects were recruited to an ongoing prospective study designed to evaluate the effect of HMG-CoA reductase inhibitors on atherosclerosis. Eligible subjects were asymptomatic individuals older than 55 years who were eligible for statin therapy. Coronary CT angiography was performed by using a 320-detector row scanner. Coronary wall thickness and plaque were evaluated in all epicardial coronary arteries greater than 2 mm in diameter. Images were analyzed by using dedicated software involving an adaptive lumen attenuation algorithm. Total plaque index (calcified plus noncalcified plaque) was defined as plaque volume divided by vessel length. Multivariable regression analysis was performed to determine the relationship between risk factors and plaque indexes. Results The mean age of the subjects was 65.5 years ± 6.9 (standard deviation) (36% women), and the median coronary artery calcium (CAC) score was 73 (interquartile range, 1-434). The total coronary plaque index was higher in men than in women (42.06 mm(2) ± 9.22 vs 34.33 mm(2) ± 8.35; P < .001). In multivariable analysis controlling for all risk factors, total plaque index remained higher in men than in women (by 5.01 mm(2); P = .03) and in those with higher simvastatin doses (by 0.44 mm(2)/10 mg simvastatin dose equivalent; P = .02). Noncalcified plaque index was positively correlated with systolic blood pressure (ß = 0.80 mm(2)/10 mm Hg; P = .03), diabetes (ß = 4.47 mm(2); P = .03), and low-density lipoprotein (LDL) cholesterol level (ß = 0.04 mm(2)/mg/dL; P = .02); the association with LDL cholesterol level remained significant (P = .02) after additional adjustment for the CAC score. Conclusion LDL cholesterol level, systolic blood pressure, and diabetes were associated with noncalcified plaque burden at coronary CT angiography in asymptomatic individuals with low-to-moderate risk. (©) RSNA, 2015 Online supplemental material is available for this article.

Part 1 - Coronary angiography with gadofosveset trisodium: a prospective feasibility study evaluating injection techniques for steady-state imaging.

BACKGROUND: The purpose of this study was to define an optimal injection protocol for 5-10 min duration navigator-based coronary MR angiography using an intravascular gadolinium-based contrast agent (GBCA), which is better suited for steady-state coronary MR angiography than conventional GBCAs. METHODS: Using projections from pharmacokinetic models of the intravascular concentration of gadofosveset, a dual-injection protocol was formulated and tested on 14 healthy human subjects. Modified Look-Locker inversion recovery (MOLLI) sequences were used for T1 mapping at 3 Tesla to evaluate the concentration of tracer in the aorta over the scanning interval. RESULTS: Pharmacokinetic models for a bolus plus slow infusion technique at a 5, 10, and 15 min steady state intravascular concentration was compared to single bolus curves. The 70 %/30 % bolus/slow infusion technique resulted in the highest intravascular concentration over a 5 min scan duration. Similarly, the 60 %/40 % bolus/slow infusion technique was projected to be ideal for image acquisition duration of 5-10 min. These models were confirmed with T1 maps on normal volunteers. Arterial-venous mixing of contrast was achieved within 90 s of the beginning of the bolus. CONCLUSIONS: Gadofosveset injection is optimized for the lowest intravascular T1 time for 5-10 min duration MR angiography by bolus injection of 60-70 % of the total dose followed by slow infusion of the remainder of the total dose. This protocol achieves rapid and prolonged steady state intravascular concentrations of the GBCA that may be useful for prolonged image acquisition, such as required for navigator-based coronary MR angiography at 3 Tesla. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01130545 NCT01130545 , registered as of May 25, 2010.

Corrigendum to "Erdheim-Chester disease with tendon and muscle involvement: Reports of a rare presentation" [Radiology Case Reports 19 (2024) 1866-1871].

[This corrects the article DOI: 10.1016/j.radcr.2024.02.009.].

Erdheim-Chester disease with tendon and muscle involvement: Reports of a rare presentation.

Erdheim-Chester disease (ECD) is a rare histiocytic disease that affects multiple systems in the body. While it typically targets long bones, cardiovascular structures, the retroperitoneum, and the central nervous system, reports of tendon and skeletal muscle involvement are scarce. This review presents 2 cases: a case of ECD involving the left Achilles tendon and left abductor hallucis, as well as an unusual manifestation of ECD in the thigh musculature. In Case 1, studies involved a 39-year-old man who initially presented with bone and pituitary involvement. An order for 18F-FDG PET/CT imaging was placed by marked swelling in the patient's left ankle and observed soft tissue fullness on foot radiographs, which revealed a soft tissue mass involving the left Achilles tendon, which arose along the tendon-muscle junction and involved the left abductor hallucis muscle. In Case 2, studies involved a 41-year-old man who initially presented with involvement of the cardiovascular system and retroperitoneum. 18F-FDG PET/CT scan showed an infiltrative right atrial mass and hypermetabolic lesion in the left external obturator muscle, extending to the left pectineus and right quadratus femoris muscle. Involvement of the Achilles tendon and skeletal muscle involvement, including left abductor hallucis muscle and medial thigh muscles, is one of the rare manifestations of ECD. Diagnostic delays were frequent due to the condition's rarity and nonspecific multisystemic symptoms. This should be considered in patients who present with myositis, tendinopathy, and bone pain and have other unexplained multisystemic problems.

Transient responses and significant toxicities of anti-CD30 CAR T cells for CD30+ lymphomas: results of a phase 1 trial.

ABSTRACT: New treatments are needed for relapsed and refractory CD30-expressing lymphomas. We developed a novel anti-CD30 chimeric antigen receptor (CAR), designated 5F11-28Z. Safety and feasibility of 5F11-28Z-transduced T cells (5F11-Ts) were evaluated in a phase 1 dose escalation clinical trial. Patients with CD30-expressing lymphomas received 300 mg/m2 or 500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine on days -5 to -3, followed by infusion of 5F11-Ts on day 0. Twenty-one patients received 5F11-T infusions. Twenty patients had classical Hodgkin lymphoma, and 1 had anaplastic large-cell lymphoma. Patients were heavily pretreated, with a median of 7 prior lines of therapy and substantial tumor burden, with a median metabolic tumor volume of 66.1 mL (range, 6.4-486.7 mL). The overall response rate was 43%; 1 patient achieved a complete remission. Median event-free survival was 13 weeks. Eleven patients had cytokine release syndrome (CRS; 52%). One patient had grade 3 CRS, and there was no grade 4/5 CRS. Neurologic toxicity was minimal. Nine patients (43%) had new-onset rashes. Two patients (9.5%) received extended courses of corticosteroids for prolonged severe rashes. Five patients (24%) had grade 3/4 cytopenias, with recovery time of ≥30 days, and 2 of these patients (9.5%) had prolonged cytopenias with courses complicated by life-threatening sepsis. The trial was halted early because of toxicity. Median peak blood CAR+ cells per µL was 26 (range, 1-513 cells per µL), but no infiltration of CAR+ cells was detected in lymph node biopsies. 5F11-Ts had low efficacy and substantial toxicities, which limit further development of 5F11-Ts. This trial was registered at www.clinicaltrials.gov as #NCT03049449.