Thomas Winkens

Hybrid Integration of Real-time US and Freehand SPECT: Proof of Concept in Patients with Thyroid Diseases

PURPOSE To report an initial experience regarding the feasibility and applicability of quasi-integrated freehand single photon emission computed tomography (SPECT)/ultrasonography (US) fusion imaging in patients with thyroid disease. MATERIALS AND METHODS Local ethics committee approval was obtained, and 34 patients were examined after giving written informed consent. After intravenous application of 75 MBq of technetium 99m pertechnetate, freehand three-dimensional SPECT was performed. Data were reconstructed and transferred to a US system. The combination of two independent positioning systems enabled real-time fusion of metabolic and morphologic information during US examination. Quality of automatic coregistration was evaluated visually, and deviation was determined by measuring the distance between the center of tracer distribution and the center of the US correlate. RESULTS All examinations were technically successful. For 18 of 34 examinations, the automatic coregistration and image fusion exhibited very good agreement, with no deviation. Only minor limitations in fusion offset occurred in 16 patients (mean offset ± standard deviation, 0.67 cm ± 0.3; range, 0.2-1.0 cm). SPECT artifacts occurred even in situations of clear thyroid findings (eg, unifocal autonomy). CONCLUSION The freehand SPECT/US fusion concept proved feasible and applicable; however, technical improvements are necessary.

Differential Diagnosis of Thyroid Nodules via Real-Time PET/Ultrasound (US) Fusion in a Case of Co-existing Medullary Thyroid Cancer and Adenoma

A 52-year-old woman presented with apparent carcinoid syndrome. Gallium 68 (Ga)-DOTATOC positron emission tomography (PET)/computed tomography (CT) found a 2.5-cm somatostatin receptor (SR)positive nodule in the left thyroid lobe. Basal serum calcitonin was 5184 ng/L, TSH was 0.63 mU/L, and free T4 was 16.98 pmol/L, so medullary thyroid cancer was suspected. Ultrasonography (Figure 1, A and B), F-fluorodeoxyglucose (FDG) PET/CT, and iodine 124 (I) PET/ CT, performed to allocate thyroid nodules to GaDOTATOC PET findings and exclude metastases, revealed an adjacent nodule 1 cm (Figures 1 and 2), believed to be adenoma. The patient provided informed consent for all procedures. To unambiguously characterize the nodules, we used a magnetic navigation system (VNav; GE Healthcare) to perform live fusion of metabolic/functional images acquired through PET and morphological images obtained with ultrasound (PET/ultrasonography) (1). Live fusion recently was reported to be a problem-solving tool in cases of unclear PET findings (2); although CT shows anatomical landmarks facilitating PET image interpretation, ultrasonography offers superior soft-tissue resolution to that of CT. Moreover, real-time coregistration allows immediate, interactive investigation. PET/CT data are acquired according to standard protocol, then loaded onto an ultrasonography system located in a separate room; images are aligned using anatomical landmarks, and three-dimensional PET/CT views are then automatically reoriented and fused to live ultrasonographic images according to ultrasound probe positioning (3) (Figure 2, A–C, and Movie 1). After thyroidectomy, histology confirmed our hypothesis regarding the lesions. Real-time fusion of PET/ultrasonography images thus differentiated an F-FDG-positive, I-negative, and SR-positive thyroid nodule, which proved to be medullary thyroid cancer, from an adjacent F-FDG-negative, I-positive, and SR-negative nodule, which turned out to be a compensated autonomous adenoma (Figure 2).

Determining tissue origin of circulating epithelial cells (CEC) in patients with differentiated thyroid cancer by real-time PCR using thyroid mRNA probes

The aim of this study is to determine whether circulating epithelial cells (CEC) detected in patients with differentiated thyroid cancer (DTC) stem from the thyroid gland. CEC have been described to increase in patients with progressive cancer disease and thus have been used as a marker of tumour cell dissemination. CEC were selected from venous blood samples of five DTC patients and analysis of thyroid-specific mRNA (i.e. Tg, TSH-R, TPO, NIS) was performed on a single cell level. 16/48 cells were positive for at least three different thyroid-mRNA transcripts, predominantly found in patients with detectable serum thyroglobulin. In conclusion, evidence was found that in patients with detectable serum thyroglobulin, most of the CECs originate from the thyroid gland. However, further investigations including a larger sample size are needed to validate the clinical impact of this method.

Multimodal evaluation of 2-D and 3-D ultrasound, computed tomography and magnetic resonance imaging in measurements of the thyroid volume using universally applicable cross-sectional imaging software: a phantom study.

A precise estimate of thyroid volume is necessary for making adequate therapeutic decisions and planning, as well as for monitoring therapy response. The goal of this study was to compare the precision of different volumetry methods. Thyroid-shaped phantoms were subjected to volumetry via 2-D and 3-D ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). The 3-D US scans were performed using sensor navigation and mechanical sweeping methods. Volumetry calculation ensued with the conventional ellipsoid model and the manual tracing method. The study confirmed the superiority of manual tracing with CT and MRI volumetry of the thyroid, but extended this knowledge also to the superiority of the 3-D US method, regardless of whether sensor navigation or mechanical sweeping is used. A novel aspect was successful use of the same universally applicable cross-imaging software for all modalities.

Assessment of Minimum 124I Activity Required in Uptake Measurements Before Radioiodine Therapy for Benign Thyroid Diseases

This study aimed to assess a hypothetical minimum administered activity of 124I required to achieve comparability between pretherapeutic radioiodine uptake (RAIU) measurements by 124I PET/CT and by 131I RAIU probe, the clinical standard. In addition, the impact of different reconstruction algorithms on 124I RAIU and the evaluation of pixel noise as a parameter for image quality were investigated. Methods: Different scan durations were simulated by different reconstruction intervals of 600-s list-mode PET datasets (including 15 intervals up to 600 s and 5 different reconstruction algorithms: filtered-backprojection and 4 iterative techniques) acquired 30 h after administration of 1 MBq of 124I. The Bland–Altman method was used to compare mean 124I RAIU levels versus mean 3-MBq 131I RAIU levels (clinical standard). The data of 37 patients with benign thyroid diseases were assessed. The impact of different reconstruction lengths on pixel noise was investigated for all 5 of the 124I PET reconstruction algorithms. A hypothetical minimum activity was sought by means of a proportion equation, considering that the length of a reconstruction interval equates to a hypothetical activity. Results: Mean 124I RAIU and 131I RAIU already showed high levels of agreement for reconstruction intervals of as short as 10 s, corresponding to a hypothetical minimum activity of 0.017 MBq of 124I. The iterative algorithms proved generally superior to the filtered-backprojection algorithm. 124I RAIU showed a trend toward higher levels than 131I RAIU if the influence of retrosternal tissue was not considered, which was proven to be the cause of a slight overestimation by 124I RAIU measurement. A hypothetical minimum activity of 0.5 MBq of 124I obtained with iterative reconstruction appeared sufficient both visually and with regard to pixel noise. Conclusion: This study confirms the potential of 124I RAIU measurement as an alternative method for 131I RAIU measurement in benign thyroid disease and suggests that reducing the administered activity is an option. CT information is particularly important in cases of retrosternal expansion. The results are relevant because 124I PET/CT allows additional diagnostic means, that is, the possibility of performing fusion imaging with ultrasound. 124I PET/CT might be an alternative, especially when hybrid 123I SPECT/CT is not available.

Unexpected diagnosis of peripheral schwannoma on 18F-fluoroethylcholine PET/CT for localization of prostate cancer recurrence and biopsy under real-time PET/ultrasound fusion guidance.

18F-Fluoroethylcholine (18F-FEC) PET/CT is well established for the detection of prostate cancer recurrence. However, its specificity is sometimes impaired by false-positive findings. In the present case, atypical cancer recurrence in the right distal lower leg was suspected on 18F-FEC PET/CT in a patient with a history of prostate cancer and an increased prostate-specific antigen level. Using a real-time PET/ultrasound fusion technique, the tumor was localized and a biopsy carried out, leading to a final diagnosis of peripheral schwannoma.

Low-Activity 124I-PET/Low-Dose CT Versus 131I Probe Measurements in Pretherapy Assessment of Radioiodine Uptake in Benign Thyroid Diseases

CONTEXT Radioiodine therapy of benign thyroid diseases requires pretherapy assessment of radioactive iodine uptake (RAIU) for reliable therapy planning. OBJECTIVE Our objective was to assess RAIU by low-activity (124)I-positron emission tomography/low-dose computed tomography ((124)I-PET/CT) in comparison with standard (131)I probe measurements. DESIGN/SETTING This prospective comparative study was conducted at the Jena University Hospital, Jena, Germany, in a referral center setting. PATIENTS A total of 79 patients with benign thyroid diseases were screened, 40 of whom met the inclusion criteria (stable TSH, free T3 and free T4 levels; no thyroid-specific medication, no iodine contamination) and 24 of whom agreed to participate by signing an informed consent. INTERVENTIONS All patients received the standard (131)I scintillation probe uptake test 30 hours after administration of 3 MBq (131)I. Seven days later, all patients were subjected to (124)I-PET/CT uptake measurement 30 hours after administration of 1 MBq (124)I. MAIN OUTCOME MEASURES The decay-corrected uptake values of both techniques were compared. Additionally, 3 different volume-of-interest-based evaluation methods in PET/CT (whole neck [WN], automatic isocontour [IC], and manually contoured [MC]) were evaluated. RESULTS The (131)I probe measurement and (124)I-PET.WN method provided very similar mean RAIU (30.7% ± 10.3%; 31.7% ± 8.9%), resulting in a significant positive correlation (r = 0.93, P < .001). Compared with (124)I-PET.WN, the (124)I-PET.IC (29.8% ± 8.6%) and the (124)I-PET.MC (24.5% ± 7.1%) demonstrated lower uptake values. CONCLUSIONS Using activities as low as 1 MBq, the (124)I-PET.WN method shows a good correlation with conventional (131)I probe measurement. Thus, (124)I-PET/CT is a suitable alternative for pretherapy RAIU evaluations. This may offer potential additional benefits such as PET/ultrasound fusion imaging and CT volumetry.

Retrospective chart analysis of incidental findings detected by 18F‐fluorodeoxyglucose‐PET/CT in patients with cutaneous malignant melanoma

: 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (FDG‐PET/CT) frequently reveals incidental findings. The present study focused on incidental FDG‐PET/CT findings in cutaneous melanoma patients, and verified their relevance with respect to further diagnostic measures and interventions.

The use of ostrich eggs for in ovo research - Making preclinical imaging research affordable and available

In ovo studies are a valuable option in preclinical research, but imaging studies are severely limited by the costs of dedicated equipment needed for small-sized eggs. We sought to verify the feasibility of using larger, ostrich, eggs (Struthio camelus) for imaging on the PET/CT scanners used for routine clinical investigations. Methods: Ostrich eggs were incubated until shortly before hatching, prepared for intravitelline venous injection of contrast medium or radiotracer, and imaged using native CT, contrast-enhanced CT, and PET/CT. Any technical adaptations that were needed to improve the outcome were noted. Results: Of the 34 eggs initially incubated, 12 became fully available for imaging of embryonal development. In ovo imaging with conventional PET/CT not only was feasible but also provided images of good quality, including on dynamic PET imaging. Conclusion: In ovo imaging with ostrich eggs and routine clinical scanners may allow broader application of this field of preclinical research, obviating costly dedicated equipment and reducing the number of animals needed for classic animal research. Further experiments are warranted to refine this novel approach, especially to reduce motion artifacts and improve monitoring of viability.

Ultrasound Fusion (SPECT/US)

This chapter is about initial experiences regarding the feasibility and applicability of quasi-integrated freehand (fh) single-photon emission computed tomography (SPECT)/ultrasonography (US) fusion imaging in patients undergoing sentinel lymph node (SLN) imaging or in patients with thyroid disease. The principles of radioguided surgery can be applied to this technology. The successful and emerging concept of hybrid imaging is applied to US imaging, resulting in a tool that combines the delivery of functional information (SLN, thyroid tissue) with excellent visualization of morphology. The medium-term goal of fhSPECT/US fusion imaging is to enhance diagnostic accuracy; however, further improvements are necessary to overcome technical limitations regarding the quality of co-registration and fhSPECT resolution.