Development of a Hybrid-Imaging-Based Prognostic Index for Metastasized-Melanoma Patients in Whole-Body 18F-FDG PET/CT and PET/MRI Data.

Besides tremendous treatment success in advanced melanoma patients, the rapid development of oncologic treatment options comes with increasingly high costs and can cause severe life-threatening side effects. For this purpose, predictive baseline biomarkers are becoming increasingly important for risk stratification and personalized treatment planning. Thus, the aim of this pilot study was the development of a prognostic tool for the risk stratification of the treatment response and mortality based on PET/MRI and PET/CT, including a convolutional neural network (CNN) for metastasized-melanoma patients before systemic-treatment initiation. The evaluation was based on 37 patients (19 f, 62 ± 13 y/o) with unresectable metastasized melanomas who underwent whole-body 18F-FDG PET/MRI and PET/CT scans on the same day before the initiation of therapy with checkpoint inhibitors and/or BRAF/MEK inhibitors. The overall survival (OS), therapy response, metastatically involved organs, number of lesions, total lesion glycolysis, total metabolic tumor volume (TMTV), peak standardized uptake value (SULpeak), diameter (Dmlesion) and mean apparent diffusion coefficient (ADCmean) were assessed. For each marker, a Kaplan−Meier analysis and the statistical significance (Wilcoxon test, paired t-test and Bonferroni correction) were assessed. Patients were divided into high- and low-risk groups depending on the OS and treatment response. The CNN segmentation and prediction utilized multimodality imaging data for a complementary in-depth risk analysis per patient. The following parameters correlated with longer OS: a TMTV < 50 mL; no metastases in the brain, bone, liver, spleen or pleura; ≤4 affected organ regions; no metastases; a Dmlesion > 37 mm or SULpeak < 1.3; a range of the ADCmean < 600 mm2/s. However, none of the parameters correlated significantly with the stratification of the patients into the high- or low-risk groups. For the CNN, the sensitivity, specificity, PPV and accuracy were 92%, 96%, 92% and 95%, respectively. Imaging biomarkers such as the metastatic involvement of specific organs, a high tumor burden, the presence of at least one large lesion or a high range of intermetastatic diffusivity were negative predictors for the OS, but the identification of high-risk patients was not feasible with the handcrafted parameters. In contrast, the proposed CNN supplied risk stratification with high specificity and sensitivity.

Comprehensive metabolic and morphologic disease characterization in systemic sclerosis: initial results using combined positron emission tomography and magnetic resonance imaging.

BACKGROUND: The aim of this study was to evaluate the role of metabolic and morphologic parameters derived from simultaneous hybrid PET/MRI in correlation to clinical criteria for an image-based characterization of musculoskeletal, esophagus and lymph node involvement in systemic sclerosis (SSc). METHODS: Between November 2013 and May 2015, simultaneous whole-body hybrid PET/MRI was performed in 13 prospectively recruited patients with SSc. A mean dose of 241.3 MBq 2-deoxy-2-[18F]fluoro-D-glucose (FDG) was injected. SUVmean and SUVmax values were measured in the spinal bone marrow, spleen, joints, muscles, fasciae, mediastinal lymph nodes and esophagus. MRI abnormalities were scored as 0 (absent), 1 (moderate) and 2 (marked). In addition, organ and skin involvement were graded with clinical sum score (CSS) and modified Rodnan skin score (mRSS), respectively. RESULTS: Results indicate positive correlations between mRSS and fascial FDG-uptake values (fascia summed SUVmax ρ=0.67; fascia summed SUVmean ρ=0.66) that performed better than the MRI sum score (ρ=0.50). Fascial FDG-uptake is also useful in the differentiation between diffuse and limited SSc. Additionally, FDG-PET detected patients with active mediastinal lymphadenopathy and MRI proved to be useful for the delineation of esophagus involvement. CONCLUSIONS: Fascial FDG-uptake has a strong correlation with mRSS and can discriminate between limited and diffuse SSc. These results and the detection of active lymphadenopathy and esophagus involvement can identify patients with advanced scleroderma. Combined PET/MRI therefore provides complementary information on the complex pathophysiology and may integrate several imaging procedures in one.

Assessment of image quality of a radiotherapy-specific hardware solution for PET/MRI in head and neck cancer patients.

BACKGROUND AND PURPOSE: Functional PET/MRI has great potential to improve radiotherapy planning (RTP). However, data integration requires imaging with radiotherapy-specific patient positioning. Here, we investigated the feasibility and image quality of radiotherapy-customized PET/MRI in head-and-neck cancer (HNC) patients using a dedicated hardware setup. MATERIAL AND METHODS: Ten HNC patients were examined with simultaneous PET/MRI before treatment, with radiotherapy and diagnostic scan setup, respectively. We tested feasibility of radiotherapy-specific patient positioning and compared the image quality between both setups by pairwise image analysis of 18F-FDG-PET, T1/T2-weighted and diffusion-weighted MRI. For image quality assessment, similarity measures including average symmetric surface distance (ASSD) of PET and MR-based tumor contours, MR signal-to-noise ratio (SNR) and mean apparent diffusion coefficient (ADC) value were used. RESULTS: PET/MRI in radiotherapy position was feasible - all patients were successfully examined. ASSD (median/range) of PET and MR contours was 0.6 (0.4-1.2) and 0.9 (0.5-1.3) mm, respectively. For T2-weighted MRI, a reduced SNR of -26.2% (-39.0--11.7) was observed with radiotherapy setup. No significant difference in mean ADC was found. CONCLUSIONS: Simultaneous PET/MRI in HNC patients using radiotherapy positioning aids is clinically feasible. Though SNR was reduced, the image quality obtained with a radiotherapy setup meets RTP requirements and the data can thus be used for personalized RTP.

Voxel-wise correlation of functional imaging parameters in HNSCC patients receiving PET/MRI in an irradiation setup.

PURPOSE: The purpose of this study was to demonstrate the feasibility of voxel-wise multiparametric characterization of head and neck squamous cell carcinomas (HNSCC) using hybrid multiparametric magnetic resonance imaging and positron emission tomography with [18F]-fluorodesoxyglucose (FDG-PET/MRI) in a radiation treatment planning setup. METHODS: Ten patients with locally advanced HNSCC were examined with a combined FDG-PET/MRI in an irradiation planning setup. The multiparametric imaging protocol consisted of FDG-PET, T2-weighted transverse short tau inversion recovery sequence (STIR) and diffusion-weighted MRI (DWI). Primary tumours were manually segmented and quantitative imaging parameters were extracted. PET standardized uptake values (SUV) and DWI apparent diffusion coefficients (ADC) were correlated on a voxel-wise level. RESULTS: Images acquired in this specialised radiotherapy planning setup achieved good diagnostic quality. Median tumour volume was 4.9 [1.1-42.1] ml. Mean PET SUV and ADC of the primary tumours were 5 ± 2.5 and 1.2 ± 0.3 10-3 mm2/s, respectively. In voxel-wise correlation between ADC values and corresponding FDG SUV of the tumours, a significant negative correlation was observed (r = -0.31 ± 0.27, p < 0.05). CONCLUSION: Multiparametric voxel-wise characterization of HNSCC is feasible using combined PET/MRI in a radiation planning setup. This technique may provide novel insights into tumour biology with regard to radiation therapy in the future.

Scan time reduction in diffusion-weighted imaging of the pancreas using a simultaneous multislice technique with different acceleration factors: How fast can we go?

OBJECTIVES: To investigate the feasibility of simultaneous multislice-accelerated diffusion-weighted imaging (sms-DWI) of the pancreas with different acceleration factors and its influence on image quality, acquisition time and apparent diffusion coefficients (ADCs) in comparison to conventional sequences. METHODS: DWI of the pancreas was performed at 1.5T in ten healthy volunteers and 20 patients with sms-accelerated echo-planar DWI using two different sms-acceleration factors of 2 and 3 (sms2/3-DWI). These DWI sequences were compared to conventional DWI (c-DWI) in terms of image quality parameters (5-point Likert scale) and ADC measurements. RESULTS: c-DWI and sms2-DWI offered equivalently high overall image quality (4 [1; 5]) with scan time reduction to one-third (c-DWI: 173 s, sms2-DWI: 56 s). Sms3-DWI showed significantly poorer overall image quality (3 [1; 5]; p < 0.0001). ADC values were significantly lower in sms3-DWI compared to c-DWI in the pancreatic body and tail (body: c-DWI 1.4 x 10-3 mm2/s, sms3-DWI 1.0 x 10-3 mm2/s, p = 0.028; tail: c-DWI 1.3 x 10-3 mm2/s and sms3-DWI 1.0 x 10-3 mm2/s, p = 0.014). CONCLUSIONS: Accelerated multislice DWI of the pancreas offers high image quality with a substantial reduction of acquisition time. Lower ADC values in multislice DWI should be considered in diagnostic reading. KEY POINTS: • Simultaneous multislice-accelerated diffusion-weighted imaging (sms-DWI) promises scan time minimisation. • Sms-DWI of the pancreas offers diagnostic image quality in volunteers and patients. • Sms-DWI with an acceleration factor of 2 offers high image quality. • Higher acceleration factors in sms-DWI do not provide sufficient diagnostic image quality. • ADC values may be lower in sms-DWI.

Self-navigated 4D cartesian imaging of periodic motion in the body trunk using partial k-space compressed sensing.

PURPOSE: To enable fast and flexible high-resolution four-dimensional (4D) MRI of periodic thoracic/abdominal motion for motion visualization or motion-corrected imaging. METHODS: We proposed a Cartesian three-dimensional k-space sampling scheme that acquires a random combination of k-space lines in the ky/kz plane. A partial Fourier-like constraint compacts the sampling space to one half of k-space. The central k-space line is periodically acquired to allow an extraction of a self-navigated respiration signal used to populate a k-space of multiple breathing positions. The randomness of the acquisition (induced by periodic breathing pattern) yields a subsampled k-space that is reconstructed using compressed sensing. Local image evaluations (coefficient of variation and slope steepness through organs) reveal information about motion resolvability. Image quality is inspected by a blinded reading. Sequence and reconstruction method are made publicly available. RESULTS: The method is able to capture and reconstruct 4D images with high image quality and motion resolution within a short scan time of less than 2 min. These findings are supported by restricted-isometry-property analysis, local image evaluation, and blinded reading. CONCLUSION: The proposed method provides a clinical feasible setup to capture periodic respiratory motion with a fast acquisition protocol and can be extended by further surrogate signals to capture additional periodic motions. Retrospective parametrization allows for flexible tuning toward the targeted applications. Magn Reson Med 78:632-644, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Diagnosing Lung Nodules on Oncologic MR/PET Imaging: Comparison of Fast T1-Weighted Sequences and Influence of Image Acquisition in Inspiration and Expiration Breath-Hold.

OBJECTIVE: First, to investigate the diagnostic performance of fast T1-weighted sequences for lung nodule evaluation in oncologic magnetic resonance (MR)/positron emission tomography (PET). Second, to evaluate the influence of image acquisition in inspiration and expiration breath-hold on diagnostic performance. MATERIALS AND METHODS: The study was approved by the local Institutional Review Board. PET/CT and MR/PET of 44 cancer patients were evaluated by 2 readers. PET/CT included lung computed tomography (CT) scans in inspiration and expiration (CTin, CTex). MR/PET included Dixon sequence for attenuation correction and fast T1-weighted volumetric interpolated breath-hold examination (VIBE) sequences (volume interpolated breath-hold examination acquired in inspiration [VIBEin], volume interpolated breath-hold examination acquired in expiration [VIBEex]). Diagnostic performance was analyzed for lesion-, lobe-, and size-dependence. Diagnostic confidence was evaluated (4-point Likert-scale; 1 = high). Jackknife alternative free-response receiver-operating characteristic (JAFROC) analysis was performed. RESULTS: Seventy-six pulmonary lesions were evaluated. Lesion-based detection rates were: CTex, 77.6%; VIBEin, 53.3%; VIBEex, 51.3%; and Dixon, 22.4%. Lobe-based detection rates were: CTex, 89.6%; VIBEin, 58.3%; VIBEex, 60.4%; and Dixon, 31.3%. In contrast to CT, inspiration versus expiration did not alter diagnostic performance in VIBE sequences. Diagnostic confidence was best for VIBEin and CTex and decreased in VIBEex and Dixon (1.2 ± 0.6; 1.2 ± 0.7; 1.5 ± 0.9; 1.7 ± 1.1, respectively). The JAFROC figure-of-merit of Dixon was significantly lower. All patients with malignant lesions were identified by CTex, VIBEin, and VIBEex, while 3 patients were false-negative in Dixon. CONCLUSION: Fast T1-weighted VIBE sequences allow for identification of patients with malignant pulmonary lesions. The Dixon sequence is not recommended for lung nodule evaluation in oncologic MR/PET patients. In contrast to CT, inspiration versus expiratory breath-hold in VIBE sequences was less crucial for lung nodule evaluation but was important for diagnostic confidence.

Defining optimal tracer activities in pediatric oncologic whole-body 18F-FDG-PET/MRI.

PURPOSE: To explore the feasibility of reducing administered tracer activities and to assess optimal activities for combined 18F-FDG-PET/MRI in pediatric oncology. METHODS: 30 18F-FDG-PET/MRI examinations were performed on 24 patients with known or suspected solid tumors (10 girls, 14 boys, age 12 ± 5.6 [1-18] years; PET scan duration: 4 min per bed position). Low-activity PET images were retrospectively simulated from the originally acquired data sets using randomized undersampling of list mode data. PET data of different simulated administered activities (0.25-2.5 MBq/kg body weight) were reconstructed with or without point spread function (PSF) modeling. Mean and maximum standardized uptake values (SUVmean and SUVmax) as well as SUV variation (SUVvar) were measured in physiologic organs and focal FDG-avid lesions. Detectability of organ structures and of focal 18F-FDG-avid lesions as well as the occurrence of false-positive PET lesions were assessed at different simulated tracer activities. RESULTS: Subjective image quality steadily declined with decreasing tracer activities. Compared to the originally acquired data sets, mean relative deviations of SUVmean and SUVmax were below 5 % at 18F-FDG activities of 1.5 MBq/kg or higher. Over 95 % of anatomic structures and all pathologic focal lesions were detectable at 1.5 MBq/kg 18F-FDG. Detectability of anatomic structures and focal lesions was significantly improved using PSF. No false-positive focal lesions were observed at tracer activities of 1 MBq/kg 18F-FDG or higher. Administration of 18F-FDG activities of 1.5 MBq/kg is, thus, feasible without obvious diagnostic shortcomings, which is equivalent to a dose reduction of more than 50 % compared to current recommendations. CONCLUSION: Significant reduction in administered 18F-FDG tracer activities is feasible in pediatric oncologic PET/MRI. Appropriate activities of 18F-FDG or other tracers for specific clinical questions have to be further established in selected patient populations.

Systematic Evaluation of Amide Proton Chemical Exchange Saturation Transfer at 3 T: Effects of Protein Concentration, pH, and Acquisition Parameters.

OBJECTIVE: The goal of this work was to systematically evaluate the reproducibility of amide proton transfer chemical exchange saturation transfer (APT-CEST) at 3 T and its signal dependence on pH, protein concentration, and acquisition parameters. An in vitro system based on bovine serum albumin (BSA) was used, and its limitations were tested by comparing it to in vivo measurements. The contribution of small endogenous metabolites on the APT-CEST signal at 3 T was also investigated. In addition, the reliability of different z-spectrum interpolations as well as the use of only a few frequency offset data points instead of a whole z-spectrum were tested. MATERIALS AND METHODS: We created both a BSA phantom at different concentrations and pH values and a metabolite phantom with different small molecules. Chemical exchange saturation transfer data were acquired using a 2-dimensional fast spoiled gradient-echo sequence with pulsed CEST preparation at different saturation durations and power levels. Healthy volunteer measurements were taken for comparison. Z-spectra were interpolated using a 24th-order polynomial (Poly), an eighth-order Fourier series (Fourier), and a smoothing Spline (sSpline) algorithm. To evaluate reduced data sets, only 6 to 14 frequency offsets of the z-spectrum were used and interpolated via a cubic Spline. Region of interest (ROI) evaluations were used to investigate the reproducibility of amide magnetization transfer ratio asymmetry [MTRasym(3.5 ppm)] and to analyze the MTRasym and z-spectra. RESULTS: Interscan standard deviations of MTRasym(3.5 ppm) were always below 0.3%. MTRasym(3.5 ppm) increased when the BSA concentrations increased and decreased when the pH increased. The amine MTRasym signal of small molecules was very small compared with BSA and was only detectable using short saturation times and higher power levels. The MTRasym(3.5 ppm) between BSA concentration steps and between nearly all pH steps was significantly different for all 3 fitting methods. The Fourier and sSpline methods showed no statistically significant differences; however, the results for the Poly method were significantly higher at some concentrations and pH values. Using only few frequency offsets resulted in less significant differences compared with fitting the complete z-spectrum. In general, MTRasym(3.5 ppm) of gray matter, white matter, and ventricle ROIs from volunteer scans increased with an increase in saturation power and partially decreased with an increase in saturation duration. Intra-ROI covariances of MTRasym(3.5 ppm) revealed the highest variations for Poly, whereas using reduced spectral data resulted in an increased signal variation. CONCLUSIONS: Amide proton transfer-CEST imaging is a highly reproducible method in which absolute signal differences of approximately 0.5% are detectable in principle. For in vivo applications, Fourier or sSpline interpolations of z-spectra are preferable. Using reduced data sets delivers similar results but with increased variation and therefore decreased (pH/concentration) differentiation capability. Differentiation capability increases with increases in the saturation duration and power level. The results from the in vitro BSA system cannot be directly transferred to the in vivo situation due to different chemical environments resulting in, for example, higher asymmetric macromolecular cMT effects in vivo. Amine signals from small molecules are unlikely to contribute to APT-CEST at 3 T (except for creatine); however, signals can be enhanced by using short saturation times and higher power levels.

Diffusion-weighted imaging in the assessment of prostate cancer: Comparison of zoomed imaging and conventional technique.

PURPOSE: To compare reduced field-of-view (zoomed) diffusion-weighted imaging (DWI) and conventional DWI in the evaluation of prostate cancer with respect to lesion detection, image quality and alignment accuracy. MATERIAL AND METHODS: The study was carried out in accordance with the Declaration of Helsinki and was approved by the institutional review board. Image data of 29 histology-proven prostate cancer lesions in 15 patients were evaluated. All patients underwent both conventional DWI and zoomed DWI at 3T. Zoomed DWI and conventional DWI sequences were analysed qualitatively and quantitatively. Subjective image quality, visual distortion and presence of artefacts were rated on a 5-point Likert scale (1=excellent) by two readers in consensus. Lesion conspicuity, sensitivity and specificity in lesion detection were evaluated and compared for both DWI sequences using ROC curves and area under the curve (AUC). To analyze the geographic distortion in DWI the alignment accuracy of prostate and lesions was measured in three spatial dimensions referring to the T2-weighted anatomical images as reference. In a region of interest (ROI) evaluation, ADC values were measured in prostate tissue and malignant lesions. Comparison of qualitative and quantitative parameters was performed using Wilcoxon test with subsequent Bonferroni correction. RESULTS: Subjective image quality was rated significantly higher in zoomed DWI compared to conventional DWI (2.1±0.9 vs. 2.7±0.9; p=0.0375). Visual distortion and artefacts were reduced in zoomed DWI without reaching statistical significance (1.8±0.7 vs. 2.4±1.0 and 2.1±1.0 vs. 2.5±1.0). Sensitivity and specificity of zoomed and conventional DWI were not significantly different. Zoomed DWI had a slightly higher AUC compared to conventional DWI without significant difference (0.82 versus 0.78; p=0.0576). Lesion conspicuity did not significantly differ between zoomed DWI and conventional DWI (1.8±0.8 vs. 1.9±1.0; p=0.8523). The alignment accuracy of zoomed DWI was significantly higher regarding both the prostate gland and lesions (deviation of outer contours of lesions in sagittal plane: 3±4mm vs. 5±3mm; p=0.0008). ADC tended to be higher in zoomed DWI without statistical significance (ADCmean in peripheral zone: 1.7±0.2×10(-3)mm(2)/s vs. 1.5±0.4×10(-3)mm(2)/s; ADCmean in lesion: 1.0±0.71×10(-3)mm(2)/s vs. 0.8±0.2×10(-3)mm(2)/s). CONCLUSIONS: Zoomed technique offers improved image quality for diffusion-weighted imaging of the prostate with reduced image distortion both for the whole gland as well as for cancer lesions and at least comparable diagnostic performance. The zoomed technique could be useful for multiparametric tissue characterization but also for biopsy and radiation therapy planning.

Scan time minimization in hepatic diffusion-weighted imaging: evaluation of the simultaneous multislice acceleration technique with different acceleration factors and gradient preparation schemes.

OBJECTIVE: To evaluate simultaneous multislice (sms) accelerated diffusion-weighted imaging (DWI) of the liver in comparison to conventional sequences. MATERIALS AND METHODS: Ten volunteers underwent DWI of the liver at 1.5 T. Four different sms-accelerated sequences with monopolar and bipolar gradient preparation (MP, BP) and acceleration factors 2 and 3 (sms2-DWI, sms3-DWI) were compared to conventional DWI (c-DWI). Image quality criteria rated on a 5-point Likert scale (5 = excellent), image quality sum scores (maximum 120), and ADC were compared using Friedman test and Dunn-Bonferroni post hoc test. Bland-Altman plots were calculated for ADC comparison. p values <0.05 were considered significant. RESULTS: Sms2-DWI offered scan time minimization of 67 % without significant difference in image quality (sum score: sms2-DWI MP/BP: 97 ± 8/92 ± 9; c-DWI MP/BP: 99 ± 8/97 ± 8). Sms3-DWI offered slight additional scan time minimization with significantly inferior image quality (sum score: sms3-DWI MP/BP: 75 ± 14/69 ± 14; p < 0.001). MP preparation provided slightly higher image quality in sms-DWI without statistical significance. ADC in sms-DWI were significantly lower (sms2-DWI MP 1.01 × 10(-3) mm(2)/s; c-DWI MP 1.20 × 10(-3) mm(2)/s; p < 0.001). CONCLUSION: Sms2-DWI provides considerable scan time minimization without significant shortcomings in image quality. Sms3-DWI provides significantly inferior image quality without further scan time minimization. Potentially lower ADC in sms-DWI should be considered in clinical routine.

Is It Possible to Detect Activated Brown Adipose Tissue in Humans Using Single-Time-Point Infrared Thermography under Thermoneutral Conditions? Impact of BMI and Subcutaneous Adipose Tissue Thickness.

PURPOSE: To evaluate the feasibility to detect activated brown adipose tissue (BAT) using single-time-point infrared thermography of the supraclavicular skin region under thermoneutral conditions. To this end, infrared thermography was compared with 18-F-FDG PET, the current reference standard for the detection of activated BAT. METHODS: 120 patients were enrolled in this study. After exclusion of 18 patients, 102 patients (44 female, 58 male, mean age 58±17 years) were included for final analysis. All patients underwent a clinically indicated 18F-FDG-PET/CT examination. Immediately prior to tracer injection skin temperatures of the supraclavicular, presternal and jugular regions were measured using spatially resolved infrared thermography at room temperature. The presence of activated BAT was determined in PET by typical FDG uptake within the supraclavicular adipose tissue compartments. Local thickness of supraclavicular subcutaneous adipose tissue (SCAT) was measured on CT. Measured skin temperatures were statistically correlated with the presence of activated BAT and anthropometric data. RESULTS: Activated BAT was detected in 9 of 102 patients (8.8%). Local skin temperature of the supraclavicular region was significantly higher in individuals with active BAT compared to individuals without active BAT. However, after statistical correction for the influence of BMI, no predictive value of activated BAT on skin temperature of the supraclavicular region could be observed. Supraclavicular skin temperature was significantly negatively correlated with supraclavicular SCAT thickness. CONCLUSION: We conclude that supraclavicular SCAT thickness influences supraclavicular skin temperature and thus makes a specific detection of activated BAT using single-time-point thermography difficult. Further studies are necessary to evaluate the possibility of BAT detection using alternative thermographic methods, e.g. dynamic thermography or MR-based thermometry taking into account BMI as a confounding factor.

Towards tracer dose reduction in PET studies: Simulation of dose reduction by retrospective randomized undersampling of list-mode data.

OBJECTIVE: Optimization of tracer dose regimes in positron emission tomography (PET) imaging is a trade-off between diagnostic image quality and radiation exposure. The challenge lies in defining minimal tracer doses that still result in sufficient diagnostic image quality. In order to find such minimal doses, it would be useful to simulate tracer dose reduction as this would enable to study the effects of tracer dose reduction on image quality in single patients without repeated injections of different amounts of tracer. The aim of our study was to introduce and validate a method for simulation of low-dose PET images enabling direct comparison of different tracer doses in single patients and under constant influencing factors. METHODS: (18)F-fluoride PET data were acquired on a combined PET/magnetic resonance imaging (MRI) scanner. PET data were stored together with the temporal information of the occurrence of single events (list-mode format). A predefined proportion of PET events were then randomly deleted resulting in undersampled PET data. These data sets were subsequently reconstructed resulting in simulated low-dose PET images (retrospective undersampling of list-mode data). This approach was validated in phantom experiments by visual inspection and by comparison of PET quality metrics contrast recovery coefficient (CRC), background-variability (BV) and signal-to-noise ratio (SNR) of measured and simulated PET images for different activity concentrations. In addition, reduced-dose PET images of a clinical (18)F-FDG PET dataset were simulated using the proposed approach. RESULTS: (18)F-PET image quality degraded with decreasing activity concentrations with comparable visual image characteristics in measured and in corresponding simulated PET images. This result was confirmed by quantification of image quality metrics. CRC, SNR and BV showed concordant behavior with decreasing activity concentrations for measured and for corresponding simulated PET images. Simulation of dose-reduced datasets based on clinical (18)F-FDG PET data demonstrated the clinical applicability of the proposed data. CONCLUSION: Simulation of PET tracer dose reduction is possible with retrospective undersampling of list-mode data. Resulting simulated low-dose images have equivalent characteristics with PET images actually measured at lower doses and can be used to derive optimal tracer dose regimes.

Simultaneous multislice diffusion-weighted MRI of the liver: Analysis of different breathing schemes in comparison to standard sequences.

PURPOSE: To systematically evaluate image characteristics of simultaneous-multislice (SMS)-accelerated diffusion-weighted imaging (DWI) of the liver using different breathing schemes in comparison to standard sequences. MATERIALS AND METHODS: DWI of the liver was performed in 10 healthy volunteers and 12 patients at 1.5T using an SMS-accelerated echo planar imaging sequence performed with respiratory-triggering and free breathing (SMS-RT, SMS-FB). Standard DWI sequences served as reference (STD-RT, STD-FB). Reduction of scan time by SMS-acceleration was measured. Image characteristics of SMS-DWI and STD-DWI with both breathing schemes were analyzed quantitatively (apparent diffusion coefficient [ADC], signal-to-noise ratio [SNR]) and qualitatively (5-point Likert scale, 5 = excellent). Qualitative and quantitative parameters were compared using Friedman test and Dunn-Bonferroni post-hoc method with P-values < 0.05 considered statistically significant. RESULTS: SMS-DWI provided diagnostic image quality in volunteers and patients both with RT and FB with a reduction of scan time of 70% (0:56 vs. 3:20 min in FB). Overall image quality did not significantly differ between FB and RT acquisition in both STD and SMS sequences (median STD-RT 5.0, STD-FB 4.5, SMS-RT: 4.75; SMS-FB: 4.5; P = 0.294). SNR in the right hepatic lobe was comparable between the four tested sequences. ADC values were significantly lower in SMS-DWI compared to STD-DWI irrespective of the breathing scheme (1.2 ± 0.2 × 10(-3) mm(2) /s vs. 1.0 ± 0.2 × 10(-3) mm(2) /s; P < 0.001). CONCLUSION: SMS-acceleration provides considerable scan time reduction for hepatic DWI with equivalent image quality compared to the STD technique both using RT and FB. Discrepancies in ADC between STD-DWI and SMS-DWI need to be considered when transferring the SMS technique to clinical routine reading. J. MAGN. RESON. IMAGING 2016;44:865-879.

Comprehensive Oncologic Imaging in Infants and Preschool Children With Substantially Reduced Radiation Exposure Using Combined Simultaneous ¹8F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging: A Direct Comparison to ¹8F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

OBJECTIVE: The aim of this study was to evaluate the clinical applicability and technical feasibility of fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) compared with FDG PET/computed tomography (CT) in young children focusing on lesion detection, PET quantification, and potential savings in radiation exposure. METHODS: Twenty examinations (10 PET/CT and 10 PET/MRI examinations) were performed prospectively in 9 patients with solid tumors (3 female, 6 male; mean age, 4.8 [1-6] years). Fluorodeoxyglucose PET/CT and FDG PET/MRI were performed sequentially after a single tracer injection. Lesion detection and analysis were performed independently in PET/CT and PET/MRI. Potential changes in diagnostic or therapeutic patient management were recorded. Positron emission tomography quantification in PET/MRI was evaluated by comparing standardized uptake values resulting from MRI-based and CT-based attenuation correction. Effective radiation doses of PET and CT were estimated. RESULTS: Twenty-one PET-positive lesions were found congruently in PET/CT and PET/MRI. Magnetic resonance imaging enabled significantly better detection of morphologic PET correlates compared with CT. Eight suspicious PET-negative lesions were identified by MRI, of which one was missed in CT. Sensitivity, specificity, and accuracy for correct lesion classification were not significantly different (90%, 47%, and 62% in PET/CT; 100%, 68%, and 79% in PET/MRI, respectively). In 4 patients, the use of PET/MRI resulted in a potential change in diagnostic management compared with PET/CT, as local and whole-body staging could be performed within 1 single examination. In 1 patient, PET/MRI initiated a change in therapeutic management. Positron emission tomography quantification using MRI-based attenuation correction was accurate compared with CT-based attenuation correction. Higher standardized uptake value deviations of about 18% were observed in the lungs due to misclassification in MRI-based attenuation maps. Potential reduction in radiation dose was 48% in PET/MRI compared with PET/CT (P < 0.05). CONCLUSIONS: FDG PET/MRI is at least equivalent to FDG PET/CT for oncologic imaging in young children. Specifically, superior soft tissue contrast of MRI results in higher confidence in lesion interpretation. Substantial savings in radiation exposure can be achieved, and the number of necessary imaging examinations can be reduced using PET/MRI compared with PET/CT.

Apparent diffusion coefficient-dependent voxelwise computed diffusion-weighted imaging: An approach for improving SNR and reducing T2 shine-through effects.

PURPOSE: To introduce and evaluate a method for signal-to-noise ratio (SNR) improvement and T2 shine-through effect reduction in diffusion-weighted magnetic resonance imaging (DWI). MATERIALS AND METHODS: The proposed method uses quantitative information given by the voxel apparent diffusion coefficient (ADC) to derive voxelwise-computed DWI (vcDWI). Behavior of signal intensity variations was simulated and correlated with measurements using a dedicated phantom for DWI allowing for independent adjustment of T2 -relaxivity and diffusivity. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were measured and compared to the method of computed DWI (cDWI). Image signal was correlated with ADCs to appreciate the extent of T2 shine-through effects. Additionally, the proposed method was retrospectively applied to whole-body DWI data of 20 patients with metastatic malignancies. vcDWI was compared to cDWI and measured DWI with respect to image quality, lesion detectability, and lesion diffusivity assessment. RESULTS: Theoretically predicted signal intensity variations showed a high correlation with measured phantom data (r > 0.96). The proposed method yielded lower background signal intensity variation and higher contrast (+144%) and CNR (+358%) for diffusion-restricted phantom compartments than cDWI. Signal intensities of vcDWI showed an increased inverse correlation with phantom ADC values compared to cDWI (r = -0.86 vs. r = -0.73). Application to patient data showed higher image quality (P < 0.001) and lesion detectability (P = 0.011) using vcDWI compared to cDWI, and higher confidence for the correct identification of diffusion-restricted lesions compared to measured DWI (80/80 vs. 60/81; P = 0.013). CONCLUSION: vcDWI is a promising approach for the reduction of T2 shine-through effects and improvement of SNR and CNR in DWI. The clinical significance of these improvements, especially regarding lesion detection, needs to be evaluated in larger prospective clinical studies.

PET/CT, MR, and PET/MR in Lymphoma and Melanoma.

With the introduction of hybrid imaging technologies such as PET/CT and recently PET/MRI, staging and therapy-response monitoring have evolved. PET/CT has been shown to be of value for routine staging of FDG-avid lymphomas before as well as at the end of treatment. For interim staging, trials are ongoing to evaluate the use of PET/CT. In melanoma, PET/CT can be recommended for stages III and IV diseases for initial staging and before surgery. Studies investigating the use of PET/CT for early therapy response are promising. The role of PET/MR in lymphoma and melanoma imaging has to be defined because no larger studies exist so far. There may be an application of PET/MR in research especially for tumor characterization and therapy response. Furthermore, the potential role of non-FDG tracers is elucidated regarding the assessment of treatment response in targeted drug regimens.

Combined unsupervised-supervised classification of multiparametric PET/MRI data: application to prostate cancer.

Multiparametric medical imaging data can be large and are often complex. Machine learning algorithms can assist in image interpretation when reliable training data exist. In most cases, however, knowledge about ground truth (e.g. histology) and thus training data is limited, which makes application of machine learning algorithms difficult. The purpose of this study was to design and implement a learning algorithm for classification of multidimensional medical imaging data that is robust and accurate even with limited prior knowledge and that allows for generalization and application to unseen data. Local prostate cancer was chosen as a model for application and validation. 16 patients underwent combined simultaneous [(11) C]-choline positron emission tomography (PET)/MRI. The following imaging parameters were acquired: T2 signal intensities, apparent diffusion coefficients, parameters Ktrans and Kep from dynamic contrast-enhanced MRI, and PET standardized uptake values (SUVs). A spatially constrained fuzzy c-means algorithm (sFCM) was applied to the single datasets and the resulting labeled data were used for training of a support vector machine (SVM) classifier. Accuracy and false positive and false negative rates of the proposed algorithm were determined in comparison with manual tumor delineation. For five of the 16 patients rates were also determined in comparison with the histopathological standard of reference. The combined sFCM/SVM algorithm proposed in this study revealed reliable classification results consistent with the histopathological reference standard and comparable to those of manual tumor delineation. sFCM/SVM generally performed better than unsupervised sFCM alone. We observed an improvement in accuracy with increasing number of imaging parameters used for clustering and SVM training. In particular, including PET SUVs as an additional parameter markedly improved classification results. A variety of applications are conceivable, especially for imaging of tissues without easily available histopathological correlation.

Multiparametric analysis of bone marrow in cancer patients using simultaneous PET/MR imaging: Correlation of fat fraction, diffusivity, metabolic activity, and anthropometric data.

BACKGROUND: To analyze the regional composition of bone marrow (BM) in correlation with metabolic activity and diffusivity using simultaneous positron emission tomography (PET)/MRI. METHODS: Retrospective analysis of 18F-FDG-PET/MR scans of 110 patients was performed. A three-dimensional gradient-echo sequence with Dixon-based fat-water separation was used for fat quantification. Dixon images, diffusion-weighted images (DWI) and 18F-FDG-PET were co-registered. Mean values of fat fraction (FF), standardized uptake value (SUV), and apparent diffusion coefficient (ADC) of BM were measured in different anatomical regions. Correlation of FF, SUV, and ADC and association of BM fat content and metabolic activity with anthropometric data was analyzed (Pearson). BM fat content and metabolic activity was compared in patients with and without chemotherapy (t-test). RESULTS: Regional differences in BM were found with highest fat content (93 ± 8%) and lowest ADC (0.22 ± 0.18 × 10(-3) mm(2) /s) in the peripheral skeleton and highest SUV in the spine (1.77 ± 0.6). There was a significant inverse correlation between FF and SUV (r = -0.73; P < 0.0001) and a significant inverse correlation between FF and ADC (r = -0.62; P < 0.0001). In patients with chemotherapy, a tendency to higher fat content and lower metabolic activity was observed in the proximal skeleton, although no statistical significance was reached. CONCLUSION: BM shows distinct regional variations in FF, SUV, and ADC. The inverse correlation of FF and SUV in BM suggests that BM adipose tissue does not have a comparable high metabolic activity as brown adipose tissue.