Assessment of left and right ventricular functional parameters using dynamic dual-tracer [13N]NH3 and [18F]FDG PET/MRI.

BACKGROUND: Cardiac positron emission tomography/magnetic resonance imaging (PET/MRI) can assess various cardiovascular diseases. In this study, we intra-individually compared right (RV) and left ventricular (LV) parameters obtained from dual-tracer PET/MRI scan. METHODS: In 22 patients with coronary heart disease (69 ± 9 years) dynamic [13N]NH3 (NH3) and [18F]FDG (FDG) PET scans were acquired. The first 2 minutes were used to calculate LV and RV first-pass ejection fraction (FPEF). Additionally, LV end-systolic (LVESV) and end-diastolic (LVEDV) volume and ejection fraction (LVEF) were calculated from the early (EP) and late-myocardial phases (LP). MRI served as a reference. RESULTS: RVFPEF and LVFPEF from FDG and NH3 as well as RVEF and LVEF from MRI were (28 ± 11%, 32 ± 15%), (32 ± 11%, 41 ± 14%) and (42 ± 16%, 45 ± 19%), respectively. LVESV, LVEDV and LVEF from EP FDG and NH3 in 8 and 16 gates were [71 (15 to 213 mL), 98 (16 to 241 mL), 32 ± 17%] and [50 (17 to 206 mL), 93 (13 to 219 mL), 36 ± 17%] as well as [60 (19 to 360 mL), 109 (56 to 384 mL), 41 ± 22%] and [54 (16 to 371 mL), 116 (57 to 431 mL), 46 ± 24%], respectively. Moreover, LVESV, LVEDV and LVEF acquired from LP FDG and NH3 were (85 ± 63 mL, 138 ± 63 mL, 47 ± 19%) and (79 ± 56 mL, 137 ± 63 mL, 47 ± 20%), respectively. The LVESV, LVEDV from MRI were 93 ± 66 mL and 153 ± 71 mL, respectively. Significant correlations were observed for RVFPEF and LVFPEF between FDG and MRI (R = .51, P = .01; R = .64, P = .001), respectively. LVESV, LVEDV, and LVEF revealed moderate to strong correlations to MRI when they acquired from EP FDG and NH3 in 16 gates (all R > .7, P = .000). Similarly, all LV parameters from LP FDG and NH3 correlated good to strongly positive with MRI (all R > .7, and P < .001), except EDV from NH3 weakly correlated to EDV of MRI (R = .54, P < .05). Generally, Bland-Altman plots showed good agreements between PET and MRI. CONCLUSIONS: Deriving LV and RV functional values from various phases of dynamic NH3 and FDG PET is feasible. These results could open a new perspective for further clinical applications of the PET examinations.

Fully Integrated PET/MR Imaging for the Assessment of the Relationship Between Functional Connectivity and Glucose Metabolic Rate.

In the past, determination of absolute values of cerebral metabolic rate of glucose (CMRGlc) in clinical routine was rarely carried out due to the invasive nature of arterial sampling. With the advent of combined PET/MR imaging technology, CMRGlc values can be obtained non-invasively, thereby providing the opportunity to take advantage of fully quantitative data in clinical routine. However, CMRGlc values display high physiological variability, presumably due to fluctuations in the intrinsic activity of the brain at rest. To reduce CMRGlc variability associated with these fluctuations, the objective of this study was to determine whether functional connectivity measures derived from resting-state fMRI (rs-fMRI) could be used to correct for these fluctuations in intrinsic brain activity. METHODS: We studied 10 healthy volunteers who underwent a test-retest dynamic [18F]FDG-PET study using a fully integrated PET/MR system (Siemens Biograph mMR). To validate the non-invasive derivation of an image-derived input function based on combined analysis of PET and MR data, arterial blood samples were obtained. Using the arterial input function (AIF), parametric images representing CMRGlc were determined using the Patlak graphical approach. Both directed functional connectivity (dFC) and undirected functional connectivity (uFC) were determined between nodes in six major networks (Default mode network, Salience, L/R Executive, Attention, and Sensory-motor network) using either a bivariate-correlation (R coefficient) or a Multi-Variate AutoRegressive (MVAR) model. In addition, the performance of a regional connectivity measure, the fractional amplitude of low frequency fluctuations (fALFF), was also investigated. RESULTS: The average intrasubject variability for CMRGlc values between test and retest was determined as (14 ±8%) with an average inter-subject variability of 25% at test and 15% at retest. The average CMRGlc value (umol/100 g/min) across all networks was 39 ±10 at test and increased slightly to 43 ±6 at retest. The R, MVAR and fALFF coefficients showed relatively large test-retest variability in comparison to the inter-subjects variability, resulting in poor reliability (intraclass correlation in the range of 0.11-0.65). More importantly, no significant relationship was found between the R coefficients (for uFC), MVAR coefficients (for dFC) or fALFF and corresponding CMRGlc values for any of the six major networks. DISCUSSION: Measurement of functional connectivity within established brain networks did not provide a means to decrease the inter- or intrasubject variability of CMRGlc values. As such, our results indicate that connectivity measured derived from rs-fMRI acquired contemporaneously with PET imaging are not suited for correction of CMRGlc variability associated with intrinsic fluctuations of resting-state brain activity. Thus, given the observed substantial inter- and intrasubject variability of CMRGlc values, the relevance of absolute quantification for clinical routine is presently uncertain.

PET/MRI versus PET/CT in oncology: a prospective single-center study of 330 examinations focusing on implications for patient management and cost considerations.

PURPOSE: PET/MRI has recently been introduced into clinical practice. We prospectively investigated the clinical impact of PET/MRI compared with PET/CT, in a mixed population of cancer patients, and performed an economic evaluation of PET/MRI. METHODS: Cancer patients referred for routine staging or follow-up by PET/CT underwent consecutive PET/CT and PET/MRI, using single applications of [18F]FDG, [68Ga]Ga-DOTANOC, or [18F]FDOPA, depending on tumor histology. PET/MRI and PET/CT were rated separately, and lesions were assessed per anatomic region; based on regions, per-examination and per-patient accuracies were determined. A simulated, multidisciplinary team meeting served as reference standard and determined whether differences between PET/CT and PET/MRI affected patient management. The McNemar tests were used to compare accuracies, and incremental cost-effectiveness ratios (ICERs) for PET/MRI were calculated. RESULTS: Two hundred sixty-three patients (330 same-day PET/CT and PET/MRI examinations) were included. PET/MRI was accurate in 319/330 examinations and PET/CT in 277/330 examinations; the respective accuracies of 97.3% and 83.9% differed significantly (P < 0.001). The additional findings on PET/MRI-mainly liver and brain metastases-had implications for patient management in 21/263 patients (8.0%). The per-examination cost was 596.97 EUR for PET/MRI and 405.95 EUR for PET/CT. ICERs for PET/MRI were 14.26 EUR per percent of diagnostic accuracy and 23.88 EUR per percent of correctly managed patients. CONCLUSIONS: PET/MRI enables more appropriate management than PET/CT in a nonnegligible fraction of cancer patients. Since the per-examination cost is about 50% higher for PET/MRI than for PET/CT, a histology-based triage of patients to either PET/MRI or PET/CT may be meaningful.

Assessment of attenuation correction for myocardial PET imaging using combined PET/MRI.

OBJECTIVE: To evaluate the frequency of artifacts in MR-based attenuation correction (AC) maps and their impact on the quantitative accuracy of PET-based flow and metabolism measurements in a cohort of consecutive heart failure patients undergoing combined PET/MR imaging. METHODS: Myocardial viability studies were performed in 20 patients following a dual-tracer protocol involving the assessment of myocardial perfusion (13N-NH3: 813 ± 86 MBq) and metabolism (18F-FDG: 335 ± 38 MBq). All acquisitions were performed using a fully-integrated PET/MR system, with standard DIXON-attenuation correction (DIXON-AC) mapping for each PET scan. All AC maps were examined for spatial misalignment with the emission data, total lung volume, susceptibility artifacts, and tissue inversion (TI). Misalignment and susceptibility artifacts were corrected using rigid co-registration and retrospective filling of the susceptibility-induced gaps, respectively. The effects of the AC artifacts were evaluated by relative difference measures and perceived changes in clinical interpretations. RESULTS: Average respiratory misalignment of (7 ± 4) mm of the PET-emission data and the AC maps was observed in 18 (90%) patients. Substantial changes in the lung volumes of the AC maps were observed in the test-retest analysis (ratio: 1.0 ± 0.2, range: 0.8-1.4). Susceptibility artifacts were observed in 10 (50%) patients, while six (30%) patients had TI artifacts. Average differences of 14 ± 10% were observed for PET images reconstructed with the artifactual AC maps. The combined artifact effects caused false-positive findings in three (15%) patients. CONCLUSION: Standard DIXON-AC maps must be examined carefully for artifacts and misalignment effects prior to AC correction of cardiac PET/MRI studies in order to avoid misinterpretation of biased perfusion and metabolism readings from the PET data.

PET/MRI-knocking on the doors of the rich and famous.

Since 2010 the portfolio of positron emission tomography (PET)-based imaging has been expanded by industry with the introduction of combined whole-body PET/MRI systems with the intent of merging PET-based molecular imaging with the strengths of MRI. PET/MRI has created a lot of hype in the scientific community but comparatively little traction in the clinic. The first years of whole-body PET/MRI were used to address inherent technical challenges; however, it is now time to make use of the full potential of this integrated imaging modality. This opinion piece highlights the continuing challenges for the clinical adoption of PET/MRI and cautions against putting too much emphasis on comparisons with clinical PET/CT. In order for PET/MRI to enter clinical practice, cross-specialty co-operation must be pursued with rigour and use-case scenarios must be propagated, following long-awaited expansion of reimbursement strategies and protocol standardization.

Technical Note: Fully-automated analysis of Jaszczak phantom measurements as part of routine SPECT quality control.

PURPOSE: Inspection and quantitative validation of tomographic imaging properties of SPECT systems, i.e., spatial resolution, contrast, and inhomogeneity must be performed in regular intervals. Typically, the modular Jaszczak phantom is used for that purpose, as it offers the possibility to investigate all three system properties with a single measurement. The interpretation of the measurement is performed visually, thus, being insensitive to subtle changes in system performance. To overcome this limitation, a fully-automated software for the objective analysis of Jaszczak phantom measurements is proposed here. METHODS: The software was developed as an ImageJ plugin and offers a number of sequential evaluation steps: automatic determination of the type of Jaszczak phantom, calculation of sector and sphere contrast, detection of ring artifacts using either the Hough transform, followed by a threshold-based decision criterion, or Student's t-test. Monte Carlo simulations were used to estimate the detectability limits for ring artifacts. RESULTS: The software successfully calculated sector and sphere contrasts and reliably determined ring artifacts present in the homogeneity part of the Jaszczak phantom, based on automatic identification of the phantom type. CONCLUSION: Given the quantitative nature of the produced output, results from one imaging system can easily be compared to another in an objective way. The advantage of the software is clearly that the information provided is objective and does not rely on the experience level of the user.

Quantitative assessment of atherosclerotic plaques on (18)F-FDG PET/MRI: comparison with a PET/CT hybrid system.

PURPOSE: PET with (18)F-FDG has the potential to assess vascular macrophage metabolism. (18)F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel (18)F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of (18)F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques. METHODS: The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with (18)F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUVmax) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated. RESULTS: Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUVmax values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3 ± 0.6 vs. 3.1 ± 0.6; P < 0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman's r = 0.67, P < 0.01). In contrast, TBRmax values of plaque lesions were similar on PET/MRI and on PET/CT (2.2 ± 0.3 vs. 2.2 ± 0.3; P = 0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman's r = 0.73, P < 0.01). Considering the increasing trend in SUVmax and TBRmax values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBRmax values may also be expected with PET/MRI compared with PET/CT. CONCLUSION: SUVmax and TBRmax values are widely accepted reference parameters for estimation of the radioactivity of atherosclerotic plaques on PET/CT. However, due to a systematic underestimation of SUVmax and TBRmax with PET/MRI, the optimal cut-off values indicating the presence of inflamed plaque tissue need to be newly defined for PET/MRI.

Inter-rater reliability and aspects of validity of the parent-infant relationship global assessment scale (PIR-GAS).

BACKGROUND: The Parent-Infant Relationship Global Assessment Scale (PIR-GAS) signifies a conceptually relevant development in the multi-axial, developmentally sensitive classification system DC:0-3R for preschool children. However, information about the reliability and validity of the PIR-GAS is rare. A review of the available empirical studies suggests that in research, PIR-GAS ratings can be based on a ten-minute videotaped interaction sequence. The qualification of raters may be very heterogeneous across studies. METHODS: To test whether the use of the PIR-GAS still allows for a reliable assessment of the parent-infant relationship, our study compared a PIR-GAS ratings based on a full-information procedure across multiple settings with ratings based on a ten-minute video by two doctoral candidates of medicine. For each mother-child dyad at a family day hospital (N = 48), we obtained two video ratings and one full-information rating at admission to therapy and at discharge. This pre-post design allowed for a replication of our findings across the two measurement points. We focused on the inter-rater reliability between the video coders, as well as between the video and full-information procedure, including mean differences and correlations between the raters. Additionally, we examined aspects of the validity of video and full-information ratings based on their correlation with measures of child and maternal psychopathology. RESULTS: Our results showed that a ten-minute video and full-information PIR-GAS ratings were not interchangeable. Most results at admission could be replicated by the data obtained at discharge. We concluded that a higher degree of standardization of the assessment procedure should increase the reliability of the PIR-GAS, and a more thorough theoretical foundation of the manual should increase its validity.

Combined PET/CT for IMRT treatment planning of NSCLC: contrast-enhanced CT images for Monte Carlo dose calculation.

PURPOSE: Combined PET/CT imaging has been proposed as an integral part of radiotherapy treatment planning (TP). Contrast-enhanced CT (ceCT) images are frequently acquired as part of the PET/CT examination to support target delineation. The aim of this dosimetric planning study was to investigate the error introduced by using a ceCT for intensity modulated radiotherapy (IMRT) TP with Monte Carlo dose calculation for non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Nine patients with NSCLC prior to chemo-RT were included in this retrospective study. For each patient non-enhanced, low-dose CT (neCT), ceCT and [(18)F]-FDG-PET emission data were acquired within a single examination. Manual contouring and TP were performed on the ceCT. An additional set of independent target volumes was auto-segmented in PET images. Dose distributions were recalculated on the neCT. Differences in dosimetric parameters were evaluated. RESULTS: Dose differences in PTV and lungs were small for all patients. The maximum difference in all PTVs when using ceCT images for dose calculation was -2.1%, whereas the mean difference was less than -1.7%. Maximum differences in the lungs ranged from -1.8% to 2.1% (mean: -0.1%). In four patients an underestimation of the maximum spinal cord dose between 2% and 3.2% was observed, but treatment plans remained clinically acceptable. CONCLUSIONS: Monte Carlo based IMRT planning for NSCLC patients using ceCT allows for correct dose calculation. A direct comparison to neCT-based treatment plans revealed only small dose differences. Therefore, ceCT-based TP is clinically safe as long as the maximum acceptable dose to organs at risk is not approached.

Child psychiatric symptoms in primary school : the second wave 4 years after preschool assessment.

OBJECTIVE: Prevalence of behavioural and emotional problems in primary school children was examined 4 years after a baseline survey at preschool age. The scope of symptoms was investigated. Due to anonymity of data only group differences between the two measurements were reported. METHOD: A representative sample of 1,481 children in fourth year primary school was assessed with the Child Behaviour Checklist (CBCL). In addition to the CBCL broadband groups of internalizing (INT) and externalizing symptoms (EXT) a third group of combined internalizing and externalizing symptoms (COM) was defined. RESULTS: The 6 month prevalence of child mental health problems at second wave was 18%-a significant increase on the previous baseline rate of 12.4%. Of those 18% of children with child mental health problems 27.3% had exclusively internalizing, 6.0% externalizing symptoms and 52.4% had combined symptoms of INT and EXT. CONCLUSION: The increasing prevalence was associated with an increase of symptoms of the broadband groups INT and COM but not EXT. The results also highlight an age and gender specific vulnerability of boys, both at preschool and primary school.

Advantages and limitations of FDG PET in the follow-up of breast cancer.

18F-Fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) has been evaluated in breast cancer for the characterisation of primary tumours, lymph node staging and the follow-up of patients after surgery, chemotherapy and/or external radiotherapy. In contrast to both the low sensitivity and moderate specificity of FDG PET in the initial detection and characterisation of breast cancer and the low lesion-based sensitivity for lymph node staging, the results from use of FDG PET in re-staging breast cancer patients are very promising. A major advantage of FDG PET imaging compared with conventional imaging is that it screens the entire patient for local recurrence, lymph node metastases and distant metastases during a single whole-body examination using a single injection of activity, with a reported average sensitivity and specificity of 96% and 77%, respectively. In most studies the sensitivity of FDG PET is higher than that of a combination of conventional imaging methods. Limitations of FDG PET in the follow-up of breast cancer patients include the relatively low detection rate of bone metastases, especially in case of the sclerotic subtype, and the relatively high rate of false positive results. The rather low specificity of FDG PET can be improved/increased by utilising combined anatomical-molecular imaging techniques, such as a PET/CT tomograph. First results using PET/CT imaging in the follow-up of breast cancer patients demonstrate increased specificity compared with FDG PET alone. Both imaging modalities, however, offer to detect recurrent and metastatic breast cancer disease at an early stage and thus continue to demonstrate the efficacy of molecular imaging in patient management, despite the limited therapeutic options in recurrent and metastatic breast cancer.