Simultaneous 68Ga-DOTATOC PET/MRI in patients with gastroenteropancreatic neuroendocrine tumors: initial results.

OBJECTIVES: The aim of this pilot study was to demonstrate the potential of simultaneously acquired 68-Gallium-DOTA-D-Phe1-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography/magnetic resonance imaging (PET/MRI) in comparison with 68Ga-DOTATOC PET/computed tomography (PET/CT) in patients with known gastroenteropancreatic neuroendocrine tumors (NETs). MATERIALS AND METHODS: Eight patients (4 women and 4 men; mean [SD] age, 54 [17] years; median, 55 years; range 25-74 years) with histopathologically confirmed NET and scheduled 68Ga-DOTATOC PET/CT were prospectively enrolled for an additional integrated PET/MRI scan. Positron emission tomography/computed tomography was performed using a triple-phase contrast-enhanced full-dose protocol. Positron emission tomography/magnetic resonance imaging encompassed a diagnostic, contrast-enhanced whole-body MRI protocol. Two readers separately analyzed the PET/CT and PET/MRI data sets including their subscans in random order regarding lesion localization, count, and characterization on a 4-point ordinal scale (0, not visible; 1, benign; 2, indeterminate; and 3, malignant). In addition, each lesion was rated in consensus on a binary scale (allowing for benign/malignant only). Clinical imaging, existing prior examinations, and histopathology (if available) served as the standard of reference. In PET-positive lesions, the standardized uptake value (SUV max) was measured in consensus. A descriptive, case-oriented data analysis was performed, including determination of frequencies and percentages in detection of malignant, benign, and indeterminate lesions in connection to their localization. In addition, percentages in detection by a singular modality (such as PET, CT, or MRI) were calculated. Interobserver variability was calculated (Cohen's κ). The SUVs in the lesions in PET/CT and PET/MRI were measured, and the correlation coefficient (Pearson, 2-tailed) was calculated. RESULTS: According to the reference standard, 5 of the 8 patients had malignant NET lesions at the time of the examination. A total of 4 patients were correctly identified by PET/CT, with the PET and CT component correctly identifying 3 patients each. All 5 patients positive for NET disease were correctly identified by PET/MRI, with the MRI subscan identifying all 5 patients and the PET subscan identifying 3 patients. All lesions considered as malignant in PET/CT were equally depicted in and considered using PET/MRI. One liver lesion rated as "indetermined" in PET/CT was identified as metastasis in PET/MRI because of a diffusion restriction in diffusion-weighted imaging. Of the 4 lung lesions characterized in PET/CT, only 1 was depicted in PET/MRI. Of the 3 lymph nodes depicted in PET/CT, only 1 was characterized in PET/MRI. Interobserver reliability was equally very good in PET/CT (κ = 0.916) and PET/MRI (κ = 1.0). The SUV max measured in PET/CT and in PET/MRI showed a strong correlation (Pearson correlation coefficient, 0.996). CONCLUSIONS: This pilot study demonstrates the potential of 68Ga-DOTATOC PET/MRI in patients with gastroenteropancreatic NET, with special advantages in the characterization of abdominal lesions yet certain weaknesses inherent to MRI, such as lung metastases and hypersclerotic bone lesions.

Standardized uptake values for [¹8F] FDG in normal organ tissues: comparison of whole-body PET/CT and PET/MRI.

PURPOSE: To compare maximum and mean standardized uptake values (SUVmax/mean) of normal organ tissues derived from [(18)F]-fluoro-desoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) using MR attenuation correction (MRAC) (DIXON-based 4-segment µ-map) with [(18)F]-FDG positron emission tomography/computed tomography (PET/CT) using CT-based attenuation correction (CTAC). METHODS AND MATERIALS: In 25 oncologic patients (15 men, 10 women; age 57 ± 13 years) after routine whole-body FDG-PET/CT (60 min after injection of 290 ± 40 MBq [(18)F]-FDG) a whole-body PET/MRI was performed (Magnetom Biograph mMR, Siemens Healthcare, Erlangen, Germany). Volumes of interest of 1.0 cm(3) were drawn in 7 physiological organ sites in MRAC-PET and the corresponding CTAC-PET images manually. Spearman correlation coefficients were calculated to compare MRAC- and CTAC based SUV values; Wilcoxon-Matched-Pairs signed ranks test was performed to test for potential differences. RESULTS: The mean delay between FDG-PET/CT and PET/MRI was 92 ± 18 min. Excellent correlations of SUV values were found for the heart muscle (SUVmax/mean: R=0.97/0.97); reasonably good correlations were found for the liver (R=0.65/0.72), bone marrow (R=0.42/0.41) and the SUVmax of the psoas muscle (R=0.41). For subcutaneous fat, the correlation coefficient was 0.66 for SUVmean (p<0.05). Correlations between MRAC and CTAC were non-significant for SUVmean of the psoas muscle, SUVmax of subcutaneous fat, SUVmax and SUVmean of the lungs, SUVmax and SUVmean of the blood-pool. The median SUVmax and SUVmean in MRAC-PET were lower than the respective CTAC values in all organs (p<0.05) but heart (SUVmax) and the bone marrow (SUVmean). CONCLUSION: In conclusion, in oncologic patients examined with PET/CT and PET/MRI SUVmax and SUVmean values generally correlate well in normal organ tissues, except the lung, subcutaneous fat and the blood pool. SUVmax and SUVmean derived from PET/MRI can be used reliably in clinical routine.

Optimizing positron emission tomography image acquisition protocols in integrated positron emission tomography/magnetic resonance imaging.

OBJECTIVES: In integrated positron emission tomography (PET)/magnetic resonance imaging (MRI), the PET data acquisition is performed simultaneously to the magnetic resonance data acquisition, leaving latitude for the duration of PET acquisition time. This establishes emission time as an important parameter in forthcoming PET/MRI protocols because it is one of the key factors determining PET image quality. Thus, the purpose of the current study was to identify optimal duration of PET acquisition time in PET/MRI. MATERIALS AND METHODS: A total of 22 consecutive patients (7 men, 15 women) underwent fluorine-18-labeled fluorodeoxyglucose (18[F]FDG) PET/MRI after clinical PET/computed tomography. Positron emission tomography/magnetic resonance scans were acquired for 8 minutes per bed position (mpb). Positron emission tomography was extracted to reconstruct images with 2, 4, 6, and 8 mpb for each patient. Visual and quantitative approaches were used to assess image quality and lesion detectability for each image. For image quality, (a) 3 readers independently scored subjective image quality on a 4-point scale and (b) a region-of-interest approach was used to obtain a quantitative estimate of image quality in terms of noise. For lesion detectability, (a) the readers independently counted the number of hypermetabolic lesions and (b) signal-to-noise ratio and contrast-to-noise ratio were computed in a region-of-interest approach. Moreover, the mean and maximal standardized uptake value (SUV mean and SUV max, respectively) of the hypermetabolic lesions was compared across all acquisition times. RESULTS: For image quality, subjective image quality significantly declined from 8 to 2 mpb (P <; 0.05), with the exception of the difference between 6 and 8 mpb. Image noise increased with shorter imaging duration, ranging from 13% on average in the 8-mpb scans to 23% in the 2-mpb scans (differences were statistically significant for 2 vs 6 mpb, 2 vs 8 mpb, and 4 vs 8 mpb; P <; 0.05). For lesion detectability, 39 hypermetabolic lesions were identified by consensus. There was no difference in detected lesions across all acquisition times. Signal-to-noise ratio and contrast-to-noise ratio were constantly high and did not differ significantly across the acquisition times. The SUV mean and SUV max did not differ significantly across all acquisition times. CONCLUSIONS: Positron emission tomography acquisition times on integrated PET/MRI do not need to exceed usual acquisition times on current PET/computed tomography scanners: Although the PET image quality suffers from short acquisition times, even a duration of 2 mpb permits sufficient lesion detection. Moreover, quantitative measures of tracer uptake are also reasonably precise at short acquisition times.

Diffusion-weighted imaging as part of hybrid PET/MRI protocols for whole-body cancer staging: does it benefit lesion detection?

PURPOSE: Positron emission tomography/magnetic resonance imaging (PET/MRI) requires efficient scan protocols for whole-body cancer staging. The aim of this study was to evaluate if the application of diffusion-weighted MR imaging (DWI) results in a diagnostic benefit for lesion detection in oncologic patients if added to a whole-body [18F]-fluorodesoxyglucose ([18F]-FDG) PET/MRI protocol. METHODS: 25 consecutive oncologic patients (16 men, 9 women; age 57 ± 12 years) prospectively underwent whole-body [18F]-FDG-PET/MRI including DWI on a hybrid PET/MRI scanner. A team of two readers assessed [18F]-FDG PET/MRI without DWI for primary tumors and metastases. In a second session, now considering DWI, readers reassessed [18F]-FDG PET/MRI accordingly. Additionally, the lesion-to-background contrast on [18F]-FDG PET and DWI was rated qualitatively (0, invisible; 1, low; 2, intermediate; 3, high). Wilcoxon's signed-rank test was performed to test for differences in the lesion-to-background contrast. RESULTS: 49 lesions were detected in 16 patients (5 primaries, 44 metastases). All 49 lesions were concordantly detected by [18F]-FDG PET/MRI alone and [18F]-FDG PET/MRI with DWI. The lesion-to-background contrast on DWI compared to [18F]-FDG PET was rated lower in 22 (44.9%) of 49 detected lesions resulting in a significantly higher lesion-to-background contrast on [18F]-FDG PET compared to DWI (P=0.001). CONCLUSIONS: DWI as part of whole-body [18F]-FDG PET/MRI does not benefit lesion detection. Given the necessity to optimize imaging protocols with regard to patient comfort and efficacy, DWI has to be questioned as a standard tool for whole-body staging in oncologic PET/MRI.

Does positron emission tomography data acquisition impact simultaneous diffusion-weighted imaging in a whole-body PET/MRI system?

OBJECTIVES: The purpose of this study was to test whether the acquisition of positron emission tomography (PET) does interfere with simultaneous diffusion weighted imaging (DWI) in an integrated whole-body PET/MRI system. MATERIAL AND METHODS: Fourteen consecutive oncological patients (9 men, 5 women; age 54 ± 13 years ([mean ± standard deviation]) scheduled for routine [(18)F]-FDG PET/CT were prospectively enrolled. For DWI, an echo planar imaging (EPI) sequence (b=0-500-1000 s/mm(2)) was acquired twice on an integrated whole-body 3T PET/MRI system in each patient; first with simultaneous PET acquisition and a second time with the PET component switched off. The apparent diffusion coefficient (ADC) and the signal-to-noise ratio at b=1000 s/mm(2) (SNR) of the myocardium, paraspinal muscle, liver, spleen, renal cortex and tumor tissue (if present) were measured. In addition, the coefficient of variation (CV) of ADC values was calculated. Student's t-test for paired samples was performed to test for differences of the mean ADC, ADC CV and SNR between DWI with and without simultaneous PET acquisition. RESULTS: There were no significant differences of the ADC [(mean ± standard deviation)] between the DWI acquisitions with and without simultaneous PET acquisition for the myocardium (2572 ± 441 × 10(-6)mm(2)/s and 2586 ± 376 × 10(-6)mm(2)/s, respectively) (P=0.817), paraspinal muscle (1279 ± 254 × 10(-6)mm(2)/s vs. 1219 ± 181 × 10(-6)mm(2)/s) (P=0.318), liver (1245 ± 158 × 10(-6)mm(2)/s vs. 1254 ± 171 × 10(-6)mm(2)/s) (P=0.848), spleen (980 ± 122 × 10(-6)mm(2)/s vs. 1000 ± 187 × 10(-6)mm(2)/s) (P=0.676) and renal cortex (1951 ± 226 × 10(-6)mm(2)/s vs. 1930 ± 273 × 10(-6)mm(2)/s) (P=0.730). Mean ADC of lymph node metastases (n=6) did not differ between with PET acquisition (853 ± 174 × 10(-6)mm(2)/s) and without simultaneous PET (865 ± 170 × 10(-6)mm(2)/s) (P=0.675). There were no significant differences between the CV of ADC values or the SNR values measured in DWI datasets that were acquired with or without simultaneous PET for any evaluated organ site. CONCLUSION: The simultaneous acquisition of DWI and PET on an integrated PET/MRI system does not impact ADC quantification of normal and tumor tissue and does not alter SNR. This knowledge provides a basis for the use of simultaneous multiparametric PET/MRI comprising DWI in diagnostic imaging and quantitative tumor therapy monitoring using repeated ADC measurements.

Pre-therapeutic blood dosimetry in patients with differentiated thyroid carcinoma using 124-iodine: predicted blood doses correlate with changes in blood cell counts after radioiodine therapy and depend on modes of TSH stimulation and number of preceding radioiodine therapies.

OBJECTIVE: Pre-therapeutic blood dosimetry prior to a high-dose radioiodine therapy (RAIT) is recommended and a blood dose of 2 Gy is considered to be safe. In this study, changes in the blood cell count after radioiodine therapy of high risk differentiated thyroid carcinoma (DTC) were analyzed and compared with the results of the pre-therapeutic blood dosimetry using 124I. Moreover, the influence of different modes of TSH stimulation and the number of preceding radioiodine therapies on the blood dose were assessed. METHODS: 198 patients with locally advanced or metastasized DTC received a pre-therapeutic blood dosimetry using 124I. To analyze the influence of the modes of TSH stimulation and the number of preceding RAITs on blood dose subgroups were built as follows: patients with endogenous TSH stimulation versus patients with exogenous TSH stimulation and patients with no preceding RAIT versus patients with at least one preceding RAIT. In 124/198 patients subsequent RAIT was performed. In 73/124 patients, hemograms were performed from day 2 to 12 month after RAIT. RESULTS: There was no high-grade bone marrow toxicity (i.e. ≥ grade 3) in patients receiving less than 2 Gy blood dose-independent of the therapeutic history. Within the first month after radioiodine therapy, there was an overall decrease in the white blood cell and platelet counts. The erythrocyte count was essentially stable. There was a correlation between cell count decrease and predicted blood doses (Spearman's correlation coefficient >-0.6 each) for the white cell line and the platelets. With regard to the subgroups, the blood dose per administered 131I activity (BDpA) was significantly higher in patients with endogenous TSH stimulation (median 0.08 Gy/GBq) than in patients with exogenous TSH stimulation (0.06 Gy/GBq) and in patients with no previous RAIT (0.08 Gy/GBq) compared to patients who had previously undergone at least one RAIT (0.07 Gy/GBq). CONCLUSIONS: The range of BDpA among DTC patients is rather wide. Our results suggest that lower blood doses can be expected when using exogenous TSH stimulation and blood doses are generally higher at first RAIT compared to subsequent RAITs. Thus, we advise to make blood dosimetry standard praxis prior to a high-activity RAIT.