Irene A. Burger

Nuclear Myocardial Perfusion Imaging with a Cadmium-Zinc-Telluride Detector Technique: Optimized Protocol for Scan Time Reduction

We aimed at establishing the optimal scan time for nuclear myocardial perfusion imaging (MPI) on an ultrafast cardiac γ-camera using a novel cadmium-zinc-telluride (CZT) solid-state detector technology. Methods: Twenty patients (17 male; BMI range, 21.7–35.5 kg/m2) underwent 1-d 99mTc-tetrofosmin adenosine stress and rest MPI protocols, each with a 15-min acquisition on a standard dual-detector SPECT camera. All scans were immediately repeated on an ultrafast CZT camera over a 6-min acquisition time and reconstructed from list-mode raw data to obtain scan durations of 1 min, 2 min, etc., up to a maximum of 6 min. For each of the scan durations, the segmental tracer uptake value (percentage of maximum myocardial uptake) from the CZT camera was compared by intraclass correlation with standard SPECT camera data using a 20-segment model, and clinical agreement was assessed per coronary territory. Scan durations above which no further relevant improvement in uptake correlation was found were defined as minimal required scan times, for which Bland–Altman limits of agreement were calculated. Results: Minimal required scan times were 3 min for low dose (r = 0.81; P < 0.001; Bland–Altman, −11.4% to 12.2%) and 2 min for high dose (r = 0.80; P < 0.001; Bland–Altman, −7.6% to 12.9%), yielding a clinical agreement of 95% and 97%, respectively. Conclusion: We have established the minimal scan time for a CZT solid-state detector system, which allows 1-d stress/rest MPI with a substantially reduced acquisition time resulting in excellent agreement with regard to uptake and clinical findings, compared with MPI from a standard dual-head SPECT γ-camera.

Whole-Body Nonenhanced PET/MR versus PET/CT in the Staging and Restaging of Cancers: Preliminary Observations

PURPOSE To assess the diagnostic performance of whole-body non-contrast material-enhanced positron emission tomography (PET)/magnetic resonance (MR) imaging and PET/computed tomography (CT) for staging and restaging of cancers and provide guidance for modality and sequence selection. MATERIALS AND METHODS This study was approved by the institutional review board and national government authorities. One hundred six consecutive patients (median age, 68 years; 46 female and 60 male patients) referred for staging or restaging of oncologic malignancies underwent whole-body imaging with a sequential trimodality PET/CT/MR system. The MR protocol included short inversion time inversion-recovery ( STIR short inversion time inversion-recovery ), Dixon-type liver accelerated volume acquisition ( LAVA liver accelerated volume acquisition ; GE Healthcare, Waukesha, Wis), and respiratory-gated periodically rotated overlapping parallel lines with enhanced reconstruction ( PROPELLER periodically rotated overlapping parallel lines with enhanced reconstruction ; GE Healthcare) sequences. Primary tumors (n = 43), local lymph node metastases (n = 74), and distant metastases (n = 66) were evaluated for conspicuity (scored 0-4), artifacts (scored 0-2), and reader confidence on PET/CT and PET/MR images. Subanalysis for lung lesions (n = 46) was also performed. Relevant incidental findings with both modalities were compared. Interreader agreement was analyzed with intraclass correlation coefficients and κ statistics. Lesion conspicuity, image artifacts, and incidental findings were analyzed with nonparametric tests. RESULTS Primary tumors were less conspicuous on STIR short inversion time inversion-recovery (3.08, P = .016) and LAVA liver accelerated volume acquisition (2.64, P = .002) images than on CT images (3.49), while findings with the PROPELLER periodically rotated overlapping parallel lines with enhanced reconstruction sequence (3.70, P = .436) were comparable to those at CT. In distant metastases, the PROPELLER periodically rotated overlapping parallel lines with enhanced reconstruction sequence (3.84) yielded better results than CT (2.88, P < .001). Subanalysis for lung lesions yielded similar results (primary lung tumors: CT, 3.71; STIR short inversion time inversion-recovery , 3.32 [P = .014]; LAVA liver accelerated volume acquisition , 2.52 [P = .002]; PROPELLER periodically rotated overlapping parallel lines with enhanced reconstruction , 3.64 [P = .546]). Readers classified lesions more confidently with PET/MR than PET/CT. However, PET/CT showed more incidental findings than PET/MR (P = .039), especially in the lung (P < .001). MR images had more artifacts than CT images. CONCLUSION PET/MR performs comparably to PET/CT in whole-body oncology and neoplastic lung disease, with the use of appropriate sequences. Further studies are needed to define regionalized PET/MR protocols with sequences tailored to specific tumor entities.

Validation of CT Attenuation Correction for High-Speed Myocardial Perfusion Imaging Using a Novel Cadmium-Zinc-Telluride Detector Technique

The aim of this study was to validate attenuation correction (AC) using low-dose standard CT for myocardial perfusion imaging (MPI) on a novel ultra fast γ-camera with cadmium-zinc-telluride (CZT) detector technology. Methods: Sixty-six patients (body mass index ± SD, 27.2 ± 3.5 kg/m2; range, 19.1–36.0 kg/m2) underwent a 1-d 99mTc-tetrofosmin adenosine stress–rest imaging protocol with 15-min acquisitions on a standard dual-head SPECT camera. All scans were repeated within minutes on the CZT camera, with 3-min acquisitions for stress (low dose) and 2-min acquisitions for rest (high dose) as recently established. We compared maximum myocardial uptake (20-segment model) from CZT versus standard SPECT MPI by intraclass correlation without and with CT AC. In addition, clinical agreement for each coronary territory for all scans from both devices was assessed, and Bland–Altmann (BA) limits of agreement for percentage uptake were calculated. Results: The clinical agreement between CZT and standard SPECT cameras was 96% for noncorrected low- and high-dose images (r = 0.90 and BA = −18 to 15, and r = 0.91 and BA = −15 to 16, respectively), and agreement after AC was 96% for low- and 99% for high-dose images (r = 0.87 and BA = −16 to 14, and r = 0.88 and BA = −16 to 14, respectively). Conclusion: Our results support that AC of MPI on the novel CZT camera, compared with AC MPI on a conventional SPECT camera, is feasible because it provides a high correlation of segmental tracer uptake and an excellent clinical agreement.

Combined pre-treatment MRI and 18F-FDG PET/CT parameters as prognostic biomarkers in patients with cervical cancer

OBJECTIVE To determine the associations of quantitative parameters derived from multiphase contrast-enhanced magnetic resonance imaging (CE-MRI), diffusion-weighted (DW) MRI and 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) with clinico-histopathological prognostic factors, disease-free survival (DFS) and overall survival (OS) in patients with cervical cancer. METHODS AND MATERIALS Our institutional review board approved this retrospective study of 49 patients (median age, 45 years) with histopathologically proven IB-IVB International Federation of Gynecology and Obstetrics (FIGO) cervical cancer who underwent pre-treatment pelvic MRI and whole-body 18F-FDG PET/CT between February 2009 and May 2012. Maximum diameter (maxTD), percentage enhancement (PE) and mean apparent diffusion coefficient (ADCmean) of the primary tumor were measured on MRI. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) were measured on 18F-FDG PET/CT. Correlations between imaging metrics and clinico-histopathological parameters including revised 2009 FIGO stage, tumor histology, grade and lymph node (LN) metastasis at diagnosis were evaluated using the Wilcoxon rank sum test. Cox modeling was used to determine associations with DFS and OS. RESULTS Median follow-up was 17 months. 41 patients (83.6%) were alive. 8 patients (16.3%) died of disease. Progression/recurrence occurred in 17 patients (34.6%). Significant differences were observed in ADCmean, SUVmax, MTV and TLG according to FIGO stage (p<0.001-0.025). There were significant correlations between ADCmean, MTV, TLG and LN metastasis (p=0.017-0.032). SUVmax was not associated with LN metastasis. FIGO stage (p=0.017/0.033), LN metastases (p=0.001/0.020), ADCmean (p=0.007/0.020) and MTV (p=0.014/0.026) were adverse predictors of both DFS/OS. maxTD (p=0.005) and TLG (p=0.024) were adverse predictors of DFS. PE and SUVmax did not correlate with DFS or OS (p=0.18-0.72). CONCLUSIONS Quantitative parameters derived from pre-treatment DW-MRI (ADCmean) and from 18F-FDG PET/CT (MTV and TLG) were associated with high-risk features and may serve as prognostic biomarkers of survival in patients with cervical cancer.

Molecular Imaging of Prostate Cancer.

Prostate cancer is the most common noncutaneous malignancy among men in the Western world. The natural history and clinical course of prostate cancer are markedly diverse, ranging from small indolent intraprostatic lesions to highly aggressive disseminated disease. An understanding of this biologic heterogeneity is considered a necessary requisite in the quest for the adoption of precise and personalized management strategies. Molecular imaging offers the potential for noninvasive assessment of the biologic interactions underpinning prostate carcinogenesis. Currently, numerous molecular imaging probes are in clinical use or undergoing preclinical or clinical evaluation. These probes can be divided into those that image increased cell metabolism, those that target prostate cancer-specific membrane proteins and receptor molecules, and those that bind to the bone matrix adjacent to metastases to bone. The increased metabolism and vascular changes in prostate cancer cells can be evaluated with radiolabeled analogs of choline, acetate, glucose, amino acids, and nucleotides. The androgen receptor, prostate-specific membrane antigen, and gastrin-releasing peptide receptor (ie, bombesin) are overexpressed in prostate cancer and can be targeted by specific radiolabeled imaging probes. Because metastatic prostate cancer cells induce osteoblastic signaling pathways of adjacent bone tissue, bone-seeking radiotracers are sensitive tools for the detection of metastases to bone. Knowledge about the underlying biologic processes responsible for the phenotypes associated with the different stages of prostate cancer allows an appropriate choice of methods and helps avoid pitfalls.

Real-time breath-hold triggering of myocardial perfusion imaging with a novel cadmium-zinc-telluride detector gamma camera

PurposeThe aim of this study was to assess the ability of real-time breath-hold-triggered myocardial perfusion imaging (MPI) using a novel cadmium-zinc-telluride (CZT) gamma camera to discriminate artefacts from true perfusion defects.MethodsA group of 40 patients underwent a 1-day 99mTc-tetrofosmin pharmacological stress/rest imaging protocol on a conventional dual detector SPECT gamma camera with and without attenuation correction (AC), immediately followed by scanning on an ultrafast CZT camera with and without real-time breath-hold triggering (instead of AC) by intermittent scanning confined to breath-hold at deep inspiration (using list mode acquisition). We studied the use of breath-hold triggering on the CZT camera and its ability to discriminate artefacts from true perfusion defects using AC SPECT MPI as the reference standard. Myocardial tracer uptake (percent of maximum) from CZT was compared to AC SPECT MPI by intraclass correlation and by calculating Bland-Altman limits of agreement.ResultsAC of SPECT MPI identified 19 apparent perfusion defects as artefacts. Of these, 13 were correctly identified and 4 were partially unmasked (decrease in extent and/or severity) by breath-hold triggering of the CZT scan. All perfusion defects verified by SPECT MPI with AC were appropriately documented by CZT with and without breath-hold triggering. This was supported by the quantitative analysis, as the correlation (r) of myocardial tracer uptake between CZT and AC SPECT improved significantly from 0.81 to 0.90 (p<0.001) when applying breath-hold triggering. Similarly, Bland-Altman limits of agreement were narrower for CZT scans with breath-hold triggering.ConclusionThis novel CZT camera allows real-time breath-hold triggering as a potential alternative to AC to assist in the discrimination of artefacts from true perfusion defects.

Dosimetry and first clinical evaluation of the new 18F-radiolabeled bombesin analogue BAY 864367 in patients with prostate cancer.

The aim of this first-in-man study was to demonstrate the feasibility, safety, and tolerability, as well as provide dosimetric data and evaluate the imaging properties, of the bombesin analogue BAY 864367 for PET/CT in a small group of patients with primary and recurrent prostate cancer (PCa). Methods: Ten patients with biopsy-proven PCa (5 with primary PCa and 5 with prostate-specific antigen recurrence after radical prostatectomy) were prospectively selected for this exploratory clinical trial with BAY 864367, a new 18F-labeled bombesin analogue. PET scans were assessed at 6 time points, up to 110 min after intravenous administration of 302 ± 11 MBq of BAY 864367. Imaging results were compared with 18F-fluorocholine PET/CT scans. Dosimetry was calculated using the OLINDA/EXM software. Results: Three of 5 patients with primary disease showed positive tumor delineation in the prostate, and 2 of 5 patients with biochemical relapse showed a lesion suggestive of recurrence on the BAY 864367 scan. Tumor-to-background ratio averaged 12.9 ± 7.0. The ratio of malignant prostate tissue to normal prostate tissue was 4.4 ± 0.6 in 3 patients with tracer uptake in the primary PCa. Mean effective dose was 4.3 ± 0.3 mSv/patient (range, 3.7–4.9 mSv). Conclusion: BAY 864367, a novel 18F-labeled bombesin tracer, was successfully investigated in a first-in-man clinical trial of PCa and showed favorable dosimetric values. Additionally, the application was safe and well tolerated. The tracer delineated tumors in a subset of patients, demonstrating the potential of gastrin-releasing-peptide receptor imaging.

TNM Staging of Non–Small Cell Lung Cancer: Comparison of PET/MR and PET/CT

The purpose of this study was to compare the diagnostic accuracy of whole-body unenhanced PET/MR with that of PET/CT in determining the stage of non–small cell lung cancer. Methods: This study was approved by the institutional review board and by national government authorities. Forty-two consecutive patients referred for the initial staging of non–small cell lung cancer underwent whole-body imaging with a sequential trimodality PET/CT/MR system. PET/MR and PET/CT datasets were evaluated separately, and a TNM stage was assigned on the basis of the image analysis. Nodal stations in the chest were identified according to the mapping system of the American Thoracic Society. The standard of reference was histopathology for the tumor stage in 20 subjects, for the nodal stage in 22 patients, and for extrathoracic metastases in 5 subjects. All other lesions were confirmed by at least 1 different imaging method. A Wilcoxon signed-ranks test was used for comparing PET/MR with PET/CT. Results: PET/MR did not provide additional information compared with PET/CT. The diagnostic accuracy of both imaging modalities was equal (T staging, P = 0.177; N staging, P = 0.114; M staging, P = 0.465), however, with advantages for PET/CT by trend. In the subgroup with histopathologic confirmation of T and N stages, the situation was similar (T staging, P = 0.705; N staging, P = 0.334). Conclusion: This study indicates that PET/MR using a fast MR protocol does not improve the diagnostic accuracy of the staging of non–small cell lung cancer.

Usefulness of Additional Coronary Calcium Scoring in Low-dose CT Coronary Angiography with Prospective ECG-Triggering: Impact on Total Effective Radiation Dose and Diagnostic Accuracy

RATIONALE AND OBJECTIVES To determine the impact of additional coronary calcium scoring on total effective radiation dose and diagnostic accuracy of low-dose computed tomography coronary angiography (CTCA) with prospective electrocardiogram (ECG) triggering. MATERIALS AND METHODS Sixty-one consecutive patients underwent 64-slice CTCA using prospective ECG triggering, calcium scoring, and invasive quantitative coronary angiography, the latter served as standard of reference. Diagnostic accuracy was calculated for CTCA, calcium scoring, and for the combination of both. Receiver operator characteristic analyses were performed to determine cutoffs for prediction of significant coronary artery stenoses. RESULTS Mean effective radiation dose was 2.1 + or - 0.7 mSv (range, 1.0-3.3 mSv) for CTCA and 1.1 + or - 0.1 mSv (range, 0.9-1.4 mSv) for calcium scoring. Per-patient sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 85.7%, 89.2%, and 100% for CTCA, and 72.7%, 82.1%, 82.8%, and 71.9% for calcium scoring. Adding calcium-scoring with a cutoff at 133 in patients aged >50.7 years with nondiagnostic CTCA improved the respective values of diagnostic accuracy of the entire study population to 100%, 96.4%, 97.1%, and 100%; the added value of calcium scoring was confined to only three patients (5%), who were reclassified from false positive to true negative. CONCLUSION Specificity and PPV of low-dose CTCA may be further improved by combining it with coronary calcium scoring. However, only a fraction of patient may benefit, whereas exposing the entire population to more than 50% increase in effective radiation dose.

Low-Dose Coronary CT Angiography With Prospective ECG Triggering: Validation of a Contrast Material Protocol Adapted to Body Mass Index

OBJECTIVE The aim of the study was to validate a body mass index (BMI)-adapted contrast material protocol to compensate for the effect of BMI on coronary attenuation during low-dose coronary CT angiography with prospective ECG triggering. MATERIALS AND METHODS One hundred forty patients underwent prospectively ECG-triggered coronary CT angiography for clinical indications. The following BMI-adapted contrast material protocol was used for imaging of 70 consecutively registered patients: BMI < 17.5, 50 mL contrast material at 4.0 mL/s; 17.5-22.4, 55 mL at 4.0 mL/s; 22.5-24.9, 65 mL at 4.0 mL/s; 25.0-27.4, 80 mL at 4.5 mL/s; 27.5-29.9, 80 mL at 5.0 mL/s; 30.0-34.9, 85 mL at 5.0 mL/s; 35.0-40.0, 95 mL at 5.0 mL/s; > 40, 105 mL at 5.0 mL/s. Seventy patients matched for BMI who had previously undergone routine coronary CT angiography with a fixed contrast material dosage of 80 mL at 5 mL/s served as the reference group. Vessel attenuation in the left main and proximal right coronary arteries was measured and correlated with BMI, and the results in the two protocol groups were compared. RESULTS The groups were well matched for BMI. The mean BMI in the nonadapted protocol group was 26.5 +/- 4.0 (standard deviation) (range, 18.9-36.5), and that in the BMI-adapted protocol group was 26.7 +/- 4.2 (range, 18.2-37.2) (p not significant). The mean amount of contrast material used was smaller in the BMI-adapted group (73.9 +/- 11.2 vs 80.0 +/- 0 mL; p < 0.01). Mean coronary artery attenuation did not differ significantly between the two groups (386 +/- 102 HU vs 385 +/- 64 HU; p not significant). Without BMI adaptation, coronary attenuation correlated strongly with BMI (r = -0.63; p < 0.001). With the BMI-adapted protocol, however, there was no correlation between BMI and coronary attenuation (r = -0.24; p not significant). CONCLUSION We validated a BMI-adapted contrast material protocol that results in adequate coronary vessel attenuation independent of individual BMI despite a significant reduction in overall amount of contrast material used.