Bart de Keizer

Quantitative Comparison of PET and Bremsstrahlung SPECT for Imaging the In Vivo Yttrium-90 Microsphere Distribution after Liver Radioembolization

Background After yttrium-90 (90Y) microsphere radioembolization (RE), evaluation of extrahepatic activity and liver dosimetry is typically performed on 90Y Bremsstrahlung SPECT images. Since these images demonstrate a low quantitative accuracy, 90Y PET has been suggested as an alternative. The aim of this study is to quantitatively compare SPECT and state-of-the-art PET on the ability to detect small accumulations of 90Y and on the accuracy of liver dosimetry. Methodology/Principal Findings SPECT/CT and PET/CT phantom data were acquired using several acquisition and reconstruction protocols, including resolution recovery and Time-Of-Flight (TOF) PET. Image contrast and noise were compared using a torso-shaped phantom containing six hot spheres of various sizes. The ability to detect extra- and intrahepatic accumulations of activity was tested by quantitative evaluation of the visibility and unique detectability of the phantom hot spheres. Image-based dose estimates of the phantom were compared to the true dose. For clinical illustration, the SPECT and PET-based estimated liver dose distributions of five RE patients were compared. At equal noise level, PET showed higher contrast recovery coefficients than SPECT. The highest contrast recovery coefficients were obtained with TOF PET reconstruction including resolution recovery. All six spheres were consistently visible on SPECT and PET images, but PET was able to uniquely detect smaller spheres than SPECT. TOF PET-based estimates of the dose in the phantom spheres were more accurate than SPECT-based dose estimates, with underestimations ranging from 45% (10-mm sphere) to 11% (37-mm sphere) for PET, and 75% to 58% for SPECT, respectively. The differences between TOF PET and SPECT dose-estimates were supported by the patient data. Conclusions/Significance In this study we quantitatively demonstrated that the image quality of state-of-the-art PET is superior over Bremsstrahlung SPECT for the assessment of the 90Y microsphere distribution after radioembolization.

The Role of Routine Diagnostic Radioiodine Whole-Body Scintigraphy in Patients with High-Risk Differentiated Thyroid Cancer

Follow-up diagnostic radioiodine whole-body scintigraphy (DxWBS) is still advised for high-risk patients with differentiated thyroid cancer. The aim of this study was to evaluate the additional value of DxWBS to stimulated thyroglobulin measurement in high-risk patients. Methods: The results of DxWBS and thyroglobulin measurements performed 6–12 mo after surgery and radioiodine thyroid remnant ablation in patients with differentiated thyroid cancer were retrospectively evaluated for 112 patients with high-risk features for recurrence (R3/T4 and N1). Results: One patient had an undetectable thyroglobulin level, with DxWBS results suggestive of cervical recurrence. DxWBS was found to be false-positive. Of the patients with detectable thyroglobulin levels, the DxWBS results were negative in 65 and positive in only 8. The 6 patients positive for thyroglobulin antibody had negative DxWBS results. The remaining patients had an undetectable thyroglobulin level and negative DxWBS results. Conclusion: Because undetectable stimulated thyroglobulin levels have a negative predictive value of 100%, DxWBS offers no information additional to recombinant human thyroid-stimulating hormone–stimulated thyroglobulin measurements in patients with high-risk differentiated thyroid cancer.

Enabling minimal invasive parathyroidectomy for patients with primary hyperparathyroidism using Tc-99m-sestamibi SPECT–CT, ultrasound and first results of 18F-fluorocholine PET–CT

OBJECTIVE Assessment of the diagnostic value of ultrasound (US), single photon-emission computed tomography-computed tomography (SPECT-CT) and (18)F-fluorocholine (FCH) PET-CT for preoperative localization of hyper-functioning parathyroid(s) in order to create a more efficient diagnostic pathway and enable minimal invasive parathyroidectomy (MIP) in patients with biochemical proven non-familial primary hyperparathyroidism (pHPT). METHODS A single-institution retrospective study of 63 consecutive patients with a biochemical diagnosis of non-familial pHPT who received a Tc-99m-sestamibi SPECT-CT and neck ultrasound. Surgical findings were used in calculating the sensitivity and the positive predictive value (PPV) of both imaging modalities. Furthermore we present 5 cases who received additional FCH PET-CT. RESULTS A total of 42 (66.7%) patients underwent MIP. The PPV and sensitivity of SPECT-CT, 93.0% and 80.3%, were significantly higher than those of US with 78.3% and 63.2%, respectively. Adding US to SPECT-CT for initial pre-operative localization did not significantly increase sensitivity but did significantly decrease PPV. Performance of US was significantly better when performed after SPECT-CT. (18)F-fluorocholine PET-CT localized the hyper-functioning parathyroid gland in 4/5 cases with discordant conventional imaging, enabling MIP. CONCLUSION SPECT-CT is the imaging modality of choice for initial pre-operative localization of hyper-functioning parathyroid gland(s) in patients with biochemical pHPT. Ultrasound should be performed after SPECT-CT for confirmation of positive SPECT-CT findings and for pre-operative marking allowing MIP. In cases with negative or discordant imaging additional FCH PET-CT should be considered since this might enable the surgeon to perform MIP.

Qualitative elastography can replace thyroid nodule fine-needle aspiration in patients with soft thyroid nodules. A systematic review and meta-analysis

CONTEXT Only a minority of thyroid nodules is malignant; nevertheless, many invasive diagnostic procedures are performed to distinguish between benign and malignant nodules. Qualitative ultrasound elastography is a non-invasive technique to evaluate thyroid nodules. OBJECTIVE To investigate the diagnostic value of qualitative elastography in distinguishing benign from malignant thyroid nodules in patients referred for fine-needle aspiration (FNA). DATA SOURCES A systematic literature search (PubMed, Embase and Cochrane Library) was performed. STUDY SELECTION Included studies reported thyroid nodule elastography color scores and the related cytologic or histologic findings in patients with a thyroid nodule referred for FNA. DATA EXTRACTION Two independent reviewers extracted study data and assessed study quality. Pooled sensitivities and specificities of different populations were calculated using a bivariate Bayesian framework. DATA SYNTHESIS Twenty studies including thyroid nodules were analyzed. Pooled results of elastography indicate a summary sensitivity of 85% (95% confidence interval [CI], 79-90%) and specificity of 80% (95% CI, 73-86%). The respective pooled negative predictive and positive predictive values were 97% (95% CI, 94-98%) and 40% (95% CI, 34-48%). The pretest probability of a benign nodule was 82%. Only 3.7% of the false-negative nodules was a follicular thyroid carcinoma. A pooled negative predictive value of 99% (95% CI, 97-100%) was found when only complete soft nodules (Asteria elastography 1) were classified as benign, which included 14% of the studied population. CONCLUSIONS Elastography has a fair specificity and sensitivity for diagnostic accuracy. Its major strength entails the detection of benignity, especially when only completely soft nodules are qualified as benign. The outcomes of our analysis show that FNA could safely be omitted in patients referred for analysis of their thyroid nodule when elastography shows it to be completely soft (Asteria elastography 1). This could prevent unnecessary invasive diagnostic procedures in a substantial portion of patients.

124I PET/CT to predict the outcome of blind 131I treatment in patients with biochemical recurrence of differentiated thyroid cancer; results of a multicenter diagnostic cohort study (THYROPET)

Patients with suspected recurrence from differentiated thyroid carcinoma, based on an increased thyroglobulin (Tg) level and negative neck ultrasound (US), pose a clinical dilemma. Because standard imaging has a low yield identifying potential recurrence, blind 131I treatment is often applied. However, a tumor-negative 131I whole-body scintigraphy (WBS) prevails in 38%–50% of patients. We performed a prospective multicenter observational cohort study to test the hypothesis that 124I PET/CT can identify the patients with a tumor-negative posttherapy 131I WBS. Methods: Our study was designed to include 100 patients with detectable Tg and a negative neck US, who were planned for blind 131I therapy. All patients underwent 124I PET/CT after administration of recombinant human thyroid-stimulating hormone. Subsequently, after 4–6 wk of thyroid hormone withdrawal patients were treated with 5.5–7.4 GBq of 131I, followed by WBS a week later. The primary endpoint was the number of 131I therapies that could have been omitted using the predicted outcome of the 124I PET/CT, operationalized as the concordance of tumor detection by 124I PET/CT, using post-131I therapy WBS as the reference test. The study would be terminated if 3 patients had a negative 124I PET/CT and a positive posttherapy 131I scan. Results: After inclusion of 17 patients, we terminated the study preliminarily because the stopping rule had been met. Median Tg level at 131I therapy was 28 μg/L (interquartile range, 129). Eight posttherapy WBS were negative (47%), all of which were correctly predicted by negative 124I PET/CT. Nine posttherapy WBS showed iodine-avid tumor, of which 4 also had positive 124I PET/CT findings. Sensitivity, specificity, negative predictive value, and positive predictive value of 124I PET/CT were 44% (confidence interval [CI], 14%–79%), 100% (CI, 63%–100%), 62% (CI, 32%–86%), and 100% (CI, 40%–100%), respectively. Implementation of 124I PET in this setting would have led to 47% (8/17) less futile 131I treatments, but 29% of patients (5/17) would have been denied potentially effective therapy. Conclusion: In patients with biochemical evidence of recurrent differentiated thyroid carcinoma and a tumor-negative neck US, the high false-negative rate of 124I PET/CT after recombinant human thyroid-stimulating hormone 124I PET/CT as implemented in this study precludes its use as a scouting procedure to prevent futile blind 131I therapy.

Modest utility of quantitative measures in (18)F-fluorodeoxyglucose positron emission tomography scanning for the diagnosis of aortic prosthetic graft infection

BACKGROUND The clinical dilemma in suspected aortic graft infection (AGI) is how to noninvasively obtain a reliable proof of infection. In addition to confirming the presence of infection, obtaining information regarding the extent of infection to select a proper strategy for reoperation is also necessary. Therefore, developing a more reliable noninvasive physiologic approach to detect infected prostheses is required. (18)F-fluorodeoxyglucose positron emission tomography scanning ((18)F-FDG PET) has been suggested to have a pivotal role in the detection of AGI. In this study, we assessed the contribution of two (semi) quantitative parameters-maximal standardized uptake value (SUVmax) and tissue-to-background ratio (TBR)-and of two visual parameters-fluorodeoxyglucose (FDG) distribution patterns and visual grading scale-in the final confirmation of the diagnosis of AGI. METHODS Patients with a central aortic prosthetic graft and symptoms clinically suggestive of AGI were gathered from a prospectively maintained database. Included were those who underwent (18)F-FDG PET scanning combined with computed tomography angiography and in whom periprosthetic samples were taken at some stage in the diagnostic process. AGI was considered proven in case of a positive culture and compared with a group with negative cultures. Positive predictive values (PPVs) and negative predictive values (NPVs) were calculated. Receiver operating characteristics curves were used to assess the ability of SUVmax and TBR to identify the presence and absence of AGI (ie, accuracy). RESULTS In 37 of 77 patients with suspected AGI, (18)FDG-PET and perigraft material for culturing was obtained. The tissue culture was positive in 21 of these 37 patients (56.7%). Mean ± standard deviation SUVmax for proven infection was 8.1 ± 3.7 (range, 3.6-18.5) and TBR was 5.9 ± 2.7 (range, 1.7-13.0). The area under the curve for SUVmax was 0.78 (95% confidence interval, 0.63-0.93). A cutoff value of 8 yielded a PPV of 80% and a NPV of 54%. The area under the curve for TBR was 0.70 (95% confidence interval, 0.52-0.87). A cutoff value of 6 yielded a PPV of 73% and NPV of 52%. The PPVs for the visual grading scale and (18)F-FDG distribution patterns were 75% and 61%, respectively; the NPVs were 77% and 67%, respectively. CONCLUSIONS Our study, performed in a small sample of patients suspected of AGI, showed that the diagnostic abilities of quantitative and visual (18)F-FDG PET parameters are modest.

Fluorine-18 fluorocholine PET-CT localizes hyperparathyroidism in patients with inconclusive conventional imaging : a multicenter study from the Netherlands

BackgroundSeveral reports have shown good performance of fluorine-18 fluorocholine (18F-FCH) PET-computed tomography (CT) for parathyroid localization, although overall evidence remains scarce. We collected data from three institutions in the Netherlands and investigated the performance of 18F-FCH PET-CT as a second-line imaging modality. Materials and methodsWe performed a retrospective review of all patients at least 18 years who underwent 18F-FCH PET-CT for biochemically proven hyperparathyroidism (HPT) and inconclusive ultrasound and sestamibi scintigraphy. Acquisition of PET images was performed 30 min after the administration of 2 MBq/kg 18F-FCH, together with a low-dose CT. ResultsPET-CT scans were performed in 33 (75%) women and 11 (25%) men with a mean age of 58.9 (range 31–80 years). Three patients had multiple endocrine neoplasia type 1, one patient had tertiary HPT because of Alport syndrome and the remaining patients had sporadic primary HPT. 18F-FCH PET-CT was positive in 34/44 (77.3%) cases. Of the 35 abnormal glands resected in 33 patients, 18F-FCH PET-CT could successfully localize 33/35 (94.3%), with only one false-positive result [positive predictive value (PPV)=97.1%]. Comparison of the 10 patients with negative PET-CT with the 34 patients with positive PET-CT showed no significant differences in age, sex, ratio of preoperative calcium, use of cinacalcet, history of neck surgery, and concomitant multinodular goiter. ConclusionOur study shows excellent performance of 18F-FCH PET-CT in patients with HPT and inconclusive conventional imaging. Because of its favorable characteristics with high performance, prospective studies should be initiated to determine whether this new technique may replace conventional sestamibi scintigraphy as a first-line imaging modality.

Whole-body MRI-DWI for assessment of residual disease after completion of therapy in lymphoma: A prospective multicenter study.

To assess the performance of whole‐body MRI including diffusion‐weighted imaging (whole‐body MRI‐DWI) for the detection of residual disease after completion of treatment in lymphoma patients.

Thyroid Ultrasound-Guided Fine-Needle Aspiration: The Positive Influence of On-Site Adequacy Assessment and Number of Needle Passes on Diagnostic Cytology Rate.

Objective: Nondiagnostic cytology is the most important limitation of thyroid ultrasound-guided fine-needle aspiration (US-FNA). This study aimed to identify factors associated with the adequacy rate of thyroid US-FNA. Study Design: Consecutive thyroid US-FNAs (2006-2013) were retrospectively included. Attending radiologists, radiology fellows and radiology residents performed US-FNA, usually involving 2-3 needle passes. In more recent years, rapid on-site adequacy assessment (ROSAA) was performed to ensure specimen adequacy. US characteristics, procedural variations and cytology results were extracted from US and pathology reports and statistically evaluated. Results: Diagnostic cytology was obtained in 64.6% of 1,381 thyroid US-FNAs. Factors associated with nondiagnostic cytology were ROSAA (74.6% diagnostic cytology, OR 0.55, 95% CI 0.42-0.71), ≥3 clinic visits for US-FNA of the same thyroid nodule (54.7%, OR 1.56, 95% CI 1.16-2.10) and increased intranodular vascularization (51.8%, OR 1.73, 95% CI 1.17-2.57). With ROSAA, an increasing number of needle passes demonstrated improving adequacy rates. The adequacy rate was not operator-dependent. Conclusion: This study demonstrates that ROSAA improves the adequacy rate of thyroid US-FNA. Without ROSAA, we recommend performing at least 3 needle passes. Less diagnostic cytology is obtained from nodules with increased intranodular vascularization or from those undergoing US-FNA ≥3 times.

18F Fluorocholine PET/MR Imaging in Patients with Primary Hyperparathyroidism and Inconclusive Conventional Imaging: A Prospective Pilot Study

Purpose To investigate the performance of flourine 18 (18F) fluorocholine (FCH) positron emission tomography (PET)/magnetic resonance (MR) imaging in patients with hyperparathyroidism and nonlocalized disease who have negative or inconclusive results at ultrasonography (US) and technetium 99m (99mTc) sestamibi scintigraphy. Materials and Methods This study was approved by the institutional review board. Between May and December 2015, 10 patients (mean age, 70.4 years; range, 58-82 years) with biochemical primary hyperparathyroidism and inconclusive results at US and 99mTc sestamibi scintigraphy were prospectively enrolled. All patients gave informed consent. Directly after administration of 3 MBq/kg of FCH, PET imaging was performed, followed by T1- and T2-weighted MR imaging before and after gadolinium enhancement. Intraoperative localization and histologic results were the reference standard for calculating sensitivity and positive predictive value. The Wilcoxon rank test was used to calculate the mean difference in maximum standardized uptake value (SUVmax) between abnormal parathyroid uptake and physiologic thyroid uptake. The Wilcoxon rank-sum test was performed. Results MR imaging alone showed true-positive lesions in five patients and a false-positive lesion in one patient. FCH PET/MR imaging allowed correct localization of nine of 10 adenomas (90% sensitivity), without any false-positive results (100% positive predictive value). One patient had four-gland hyperplasia, of which three hyperplastic glands were not localized. The median SUVmax of the nine preoperatively identified adenomas was 4.9 (interquartile range, 2.45-7.35), which was significantly higher than the SUV, 2.7 (interquartile range, 1.6-3.8), of the thyroid (P = .008). Conclusion FCH PET/MR imaging allowed localization of adenomas with high accuracy when conventional imaging results were inconclusive and provided detailed anatomic information. More patients must be examined to confirm our initial results, and the accuracy of FCH PET/MR imaging for localization of glands in patients with four-gland hyperplasia remains to be investigated.