A Macrocyclic Hybrid PET/MRI Probe for Quantitative Perfusion Imaging In Vivo.

Perfusion dynamics play a vital role in delivering essential nutrients and oxygen to tissues while removing metabolic waste products. Imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) use contrast agents to visualize perfusion and clearance patterns; however, each technique has specific limitations. Hybrid PET/MRI combines the quantitative power and sensitivity of PET with the high functional and anatomical detail of MRI and holds great promise for precision in molecular imaging. However, the development of dual PET/MRI probes has been hampered by challenging synthesis and radiolabeling. Here, we present a novel PET/MRI probe, [18F][Gd(FL1)], which exhibits excellent stability comparable to macrocyclic MRI contrast agents used in clinical practice. The unique molecular design of [18F][Gd(FL1)] allows selective and expeditious radiolabeling of the gadolinium chelate in the final synthetic step. Leveraging the strengths of MRI and PET signals, the probe enables quantitative in vivo mapping of perfusion and excretion dynamics through an innovative voxel-based analysis. The diagnostic capabilities of [18F][Gd(FL1)] were demonstrated in a pilot study on healthy mice, successfully detecting early cases of unilateral renal dysfunction. This study introduces a new approach for PET/MRI and emphasizes a streamlined probe design for improved diagnostic accuracy.

Association between gene expression and functional-metabolic architecture in Parkinson's disease.

Gene expression plays a critical role in the pathogenesis of Parkinson's disease (PD). How gene expression profiles are correlated with functional-metabolic architecture remains obscure. We enrolled 34 PD patients and 25 age-and-sex-matched healthy controls for simultaneous 18 F-FDG-PET/functional MRI scanning during resting state. We investigated the functional gradients and the ratio of standard uptake value. Principal component analysis was used to further combine the functional gradients and glucose metabolism into functional-metabolic architecture. Using partial least squares (PLS) regression, we introduced the transcriptomic data from the Allen Institute of Brain Sciences to identify gene expression patterns underlying the affected functional-metabolic architecture in PD. Between-group comparisons revealed significantly higher gradient variation in the visual, somatomotor, dorsal attention, frontoparietal, default mode, and subcortical network (pFDR < .048) in PD. Increased FDG-uptake was found in the somatomotor and ventral attention network while decreased FDG-uptake was found in the visual network (pFDR < .008). Spatial correlation analysis showed consistently affected patterns of functional gradients and metabolism (p = 2.47 × 10-8 ). PLS analysis and gene ontological analyses further revealed that genes were mainly enriched for metabolic, catabolic, cellular response to ions, and regulation of DNA transcription and RNA biosynthesis. In conclusion, our study provided genetic pathological mechanism to explain imaging-defined brain functional-metabolic architecture of PD.

Hybrid PET/MRI in Cerebral Glioma: Current Status and Perspectives.

Advanced MRI methods and PET using radiolabelled amino acids provide valuable information, in addition to conventional MR imaging, for brain tumour diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumour progression from treatment-related changes, and the early assessment of responses to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing, and has been addressed in numerous studies. Currently, most radiology and nuclear medicine departments perform these examinations independently of each other, leading to multiple examinations for the patient. The advent of hybrid PET/MRI allowed a convergence of the methods, but to date simultaneous imaging has reached little relevance in clinical neuro-oncology. This is partly due to the limited availability of hybrid PET/MRI scanners, but is also due to the fact that PET is a second-line examination in brain tumours. PET is only required in equivocal situations, and the spatial co-registration of PET examinations of the brain to previous MRI is possible without disadvantage. A key factor for the benefit of PET/MRI in neuro-oncology is a multimodal approach that provides decisive improvements in the diagnostics of brain tumours compared with a single modality. This review focuses on studies investigating the diagnostic value of combined amino acid PET and 'advanced' MRI in patients with cerebral gliomas. Available studies suggest that the combination of amino acid PET and advanced MRI improves grading and the histomolecular characterisation of newly diagnosed tumours. Few data are available concerning the delineation of tumour extent. A clear additive diagnostic value of amino acid PET and advanced MRI can be achieved regarding the differentiation of tumour recurrence from treatment-related changes. Here, the PET-guided evaluation of advanced MR methods seems to be helpful. In summary, there is growing evidence that a multimodal approach can achieve decisive improvements in the diagnostics of cerebral gliomas, for which hybrid PET/MRI offers optimal conditions.

Utility of hybrid PET/MRI in stereoelectroencephalography guided radiofrequency thermocoagulation in MRI negative epilepsy patients.

Introduction: Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) is a novel advanced non-invasive presurgical examination tool for patients with drug-resistant epilepsy (DRE). This study aims to evaluate the utility of PET/MRI in patients with DRE who undergo stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RFTC). Methods: This retrospective study included 27 patients with DRE who underwent hybrid PET/MRI and SEEG-guided RFTC. Surgery outcome was assessed using a modified Engel classification, 2 years after RFTC. Potential areas of the seizure onset zone (SOZ) were identified on PET/MRI and confirmed by SEEG. Results: Fifteen patients (55%) became seizure-free after SEEG-guided RFTC. Engel class II, III, and IV were achieved in six, two, and four patients, respectively at the 2 years follow-up. MRI was negative in 23 patients and structural abnormalities were found in four patients. Hybrid PET/MRI contributed to the identification of new structural or metabolic lesions in 22 patients. Concordant results between PET/MRI and SEEG were found in 19 patients in the identification of SOZ. Among the patients with multifocal onset, seizure-free status was achieved in 50% (6/12). Conclusion: SEEG-guided RFTC is an effective and safe treatment for drug-resistant epilepsy. Hybrid PET/MRI serves as a useful tool for detecting the potential SOZs in MRI-negative patients and guide the implantation of SEEG electrodes. Patients with multifocal epilepsy may also benefit from this palliative treatment.

Distribution of α2-Adrenergic Receptors in the Living Human Brain Using [11C]yohimbine PET.

The neurofunctional basis of the noradrenergic (NA) system and its associated disorders is still very incomplete because in vivo imaging tools in humans have been missing up to now. Here, for the first time, we use [11C]yohimbine in a large sample of subjects (46 healthy volunteers, 23 females, 23 males; aged 20-50) to perform direct quantification of regional alpha 2 adrenergic receptors' (α2-ARs) availability in the living human brain. The global map shows the highest [11C]yohimbine binding in the hippocampus, the occipital lobe, the cingulate gyrus, and the frontal lobe. Moderate binding was found in the parietal lobe, thalamus, parahippocampus, insula, and temporal lobe. Low levels of binding were found in the basal ganglia, the amygdala, the cerebellum, and the raphe nucleus. Parcellation of the brain into anatomical subregions revealed important variations in [11C]yohimbine binding within most structures. Strong heterogeneity was found in the occipital lobe, the frontal lobe, and the basal ganglia, with substantial gender effects. Mapping the distribution of α2-ARs in the living human brain may prove useful not only for understanding the role of the NA system in many brain functions, but also for understanding neurodegenerative diseases in which altered NA transmission with specific loss of α2-ARs is suspected.

Disassociation between fluctuation shift over frequency and glucose metabolism in motor cortex of Parkinson's disease: a hybrid PET/fMRI study.

Increased glucose metabolism and decreased low-frequency fluctuation have been consistently reported in the motor area of Parkinson's disease (PD). The reason for such seeming paradox is unclear. Here, we enrolled 34 PD patients and 25 healthy controls (HCs) for hybrid PET/fMRI scan (PET/fMRI(discovery) dataset). In addition, 2 replication datasets, namely fMRI(validation-1) and fMRI(validation-2) dataset, were also included. We computed ratio of standard uptake value (SUVr) to measure FDG-uptake. The amplitude of low-frequency fluctuations (ALFF) for the following 4 frequency bands was calculated: slow-5, slow-4, slow-3, and slow-2. We obtained a significant group-by-frequency interaction effect of ALFF in the paracentral lobule/supplementary motor area (PFWE = 0.003) and the right sensorimotor area (PFWE < 0.001) in the PET/fMRI(discovery) dataset, which could be replicated using fMRI(validation-1) and fMRI(validation-2) datasets (PFWE < 0.05). In detail, HCs exhibited power law-like fluctuation pattern, but PD patients did not. Correlation analyses further revealed significant associations between ALFF and FDG-uptake in HCs (P-values < 0.031), but not in PD (P-values > 0.28). Taken together, this study identified a fluctuation shift over frequency effect in PD patients, which further disassociated with glucose metabolism in the motor cortex.

Severity-dependent functional connectome and the association with glucose metabolism in the sensorimotor cortex of Parkinson's disease.

Functional MRI studies have achieved promising outcomes in revealing abnormal functional connectivity in Parkinson's disease (PD). The primary sensorimotor area (PSMA) received a large amount of attention because it closely correlates with motor deficits. While functional connectivity represents signaling between PSMA and other brain regions, the metabolic mechanism behind PSMA connectivity has rarely been well established. By introducing hybrid PET/MRI scanning, the current study enrolled 33 advanced PD patients during medication-off condition and 25 age-and-sex-matched healthy controls (HCs), aiming to not only identify the abnormal functional connectome pattern of the PSMA, but also to simultaneously investigate how PSMA functional connectome correlates with glucose metabolism. We calculated degree centrality (DC) and the ratio of standard uptake value (SUVr) using resting state fMRI and 18F-FDG-PET data. A two-sample t-test revealed significantly decreased PSMA DC (PFWE < 0.014) in PD patients. The PSMA DC also correlated negatively with H-Y stage (P = 0.031). We found a widespread reduction of H-Y stage associated (P-values < 0.041) functional connectivity between PSMA and the visual network, attention network, somatomotor network, limbic network, frontoparietal network as well as the default mode network. The PSMA DC correlated positively with FDG-uptake in the HCs (P = 0.039) but not in the PD patients (P > 0.44). In summary, we identified disease severity-dependent PSMA functional connectome which in addition uncoupled with glucose metabolism in PD patients. The current study highlighted the critical role of simultaneous PET/fMRI in revealing the functional-metabolic mechanism in the PSMA of PD patients.

Use of multimodality imaging, histology, and treatment feasibility to characterize a transgenic Rag2-null rat model of glioblastoma.

Many drugs that show potential in animal models of glioblastoma (GBM) fail to translate to the clinic, contributing to a paucity of new therapeutic options. In addition, animal model development often includes histologic assessment, but multiparametric/multimodality imaging is rarely included despite increasing utilization in patient cancer management. This study developed an intracranial recurrent, drug-resistant, human-derived glioblastoma tumor in Sprague-Dawley Rag2-Rag2 tm1Hera knockout rat and was characterized both histologically and using multiparametric/multimodality neuroimaging. Hybrid 18F-fluoroethyltyrosine positron emission tomography and magnetic resonance imaging, including chemical exchange saturation transfer (18F-FET PET/CEST MRI), was performed for full tumor viability determination and characterization. Histological analysis demonstrated human-like GBM features of the intracranially implanted tumor, with rapid tumor cell proliferation (Ki67 positivity: 30.5 ± 7.8%) and neovascular heterogeneity (von Willebrand factor VIII:1.8 to 5.0% positivity). Early serial MRI followed by simultaneous 18F-FET PET/CEST MRI demonstrated consistent, predictable tumor growth, with exponential tumor growth most evident between days 35 and 49 post-implantation. In a second, larger cohort of rats, 18F-FET PET/CEST MRI was performed in mature tumors (day 49 post-implantation) for biomarker determination, followed by evaluation of single and combination therapy as part of the model development and validation. The mean percentage of the injected dose per mL of 18F-FET PET correlated with the mean %CEST (r = 0.67, P < 0.05), but there was also a qualitative difference in hot spot location within the tumor, indicating complementary information regarding the tumor cell demand for amino acids and tumor intracellular mobile phase protein levels. Finally, the use of this glioblastoma animal model for therapy assessment was validated by its increased overall survival after treatment with combination therapy (temozolomide and idasanutlin) (P < 0.001). Our findings hold promise for a more accurate tumor viability determination and novel therapy assessment in vivo in a recently developed, reproducible, intracranial, PDX GBM.

Attenuation correction for PET/MRI to measure tracer activity surrounding total knee arthroplasty.

BACKGROUND: Positron emission tomography (PET) in combination with magnetic resonance imaging (MRI) could allow inflammatory complications near total knee arthroplasty (TKA) to be studied early in their development. However, attenuation of the PET signal by the metal TKA implants imparts substantial error into measurements of tracer activity, and conventional MR-based attenuation correction (AC) methods have large signal voids in the vicinity of metal implants. PURPOSE: To evaluate a segmentation-based AC approach to measure tracer uptake from PET/MRI scans near TKA implants. METHODS: A TKA implant (Triathlon, Stryker, Mahwah, USA) was implanted into a cadaver. Four vials were filled with [18F]fluorodeoxyglucose with known activity concentration (4.68 MBq total, 0.76 MBq/mL) and inserted into the knee. Images of the knee were acquired using a 3T PET/MRI system (Biograph mMR, Siemens Healthcare, Erlangen, Germany). Models of the implant components were registered to the MR data using rigid-body transformations and the other tissue classes were manually segmented. These segments were used to create the segmentation-based map and complete the AC. Percentage error of the resulting measured activities was calculated by comparing the measured and known amounts of activity in each vial. RESULTS: The original AC resulted in a percentage error of 64.1% from the known total activity. Errors in the individual vial activities ranged from 40.2 to 82.7%. Using the new segmentation-based AC, the percentage error of the total activity decreased to 3.55%. Errors in the individual vials were less than 15%. CONCLUSIONS: The segmentation-based AC technique dramatically reduced the error in activity measurements that result from PET signal attenuation by the metal TKA implant. This approach may be useful to enhance the reliability of PET/MRI measurements for numerous applications.

Simultaneous PET/fMRI Detects Distinctive Alterations in Functional Connectivity and Glucose Metabolism of Precuneus Subregions in Alzheimer's Disease.

As a central hub in the interconnected brain network, the precuneus has been reported showing disrupted functional connectivity and hypometabolism in Alzheimer's disease (AD). However, as a highly heterogeneous cortical structure, little is known whether individual subregion of the precuneus is uniformly or differentially involved in the progression of AD. To this end, using a hybrid PET/fMRI technique, we compared resting-state functional connectivity strength (FCS) and glucose metabolism in dorsal anterior (DA_pcu), dorsal posterior (DP_pcu) and ventral (V_pcu) subregions of the precuneus among 20 AD patients, 23 mild cognitive impairment (MCI) patients, and 27 matched cognitively normal (CN) subjects. The sub-parcellation of precuneus was performed using a K-means clustering algorithm based on its intra-regional functional connectivity. For the whole precuneus, decreased FCS (p = 0.047) and glucose hypometabolism (p = 0.006) were observed in AD patients compared to CN subjects. For the subregions of the precuneus, decreased FCS was found in DP_pcu of AD patients compared to MCI patients (p = 0.011) and in V_pcu for both MCI (p = 0.006) and AD (p = 0.008) patients compared to CN subjects. Reduced glucose metabolism was found in DP_pcu of AD patients compared to CN subjects (p = 0.038) and in V_pcu of AD patients compared to both MCI patients (p = 0.045) and CN subjects (p < 0.001). For both FCS and glucose metabolism, DA_pcu remained relatively unaffected by AD. Moreover, only in V_pcu, disruptions in FCS (r = 0.498, p = 0.042) and hypometabolism (r = 0.566, p = 0.018) were significantly correlated with the cognitive decline of AD patients. Our results demonstrated a distinctively disrupted functional and metabolic pattern from ventral to dorsal precuneus affected by AD, with V_pcu and DA_pcu being the most vulnerable and conservative subregion, respectively. Findings of this study extend our knowledge on the differential roles of precuneus subregions in AD.

Evaluation of Hybrid PET/MRI for Gross Tumor Volume (GTV) Delineation in Colorectal Cancer Liver Metastases Radiotherapy.

PURPOSE: Hybrid PET/MRI has been increasingly incorporated into the practice of radiation oncologists since it contains both anatomical and biological data and may bring about personalized radiation plans for each patient. The objective of this study was to evaluate the feasibility of GTV delineation from hybrid PET/MRI compared with that from current-practice MRI during radiotherapy planning in patients with colorectal liver metastases. PATIENTS AND METHODS: Twenty-four patients (thirty lesions) with colorectal liver metastases were prospectively enrolled in this study. Three physicians delineated the target volume with the most popular delineating methods-the visual method. First of all, differences among the three observers were assessed. The difference and correlation of GTV values obtained by MRI, PET, and hybrid PET/MRI were subjected to statistical analysis afterwards. Finally, the dice similarity coefficient (DSC) was calculated to assess the spatial overlap. Based on the value of DSC, we also evaluate the correlation between DSC and tumor size. GTV-MRI was set as a reference. RESULTS: There was no significant difference among observers in GTV-MRI (F=0.118, p=0.889), GTV-PET (F=0.070, p=0.933) and GTV-PET/MRI (F=0.40, p=0.961). 83.33% of GTV-PET/MRI and 63.33% of GTV-PET were larger than the reference GTV-MRI. Statistical analysis revealed that GTV-PET/MRI (p<0.001) and GTV-PET (p<0.05) diverged statistically significantly from GTV-MRI. GTV-PET (r=0.992, p<0.001) and GTV-PET/MRI (r=0.997, p<0.001) were significantly related to GTV-MRI. The average DSC value between GTV-MRI and GTV-PET was 0.51 (range 0-0.90) and that between GTV-MRI and GTV-PET/MRI was 0.72 (range 0.42-0.90). There was a positive correlation between the DSC and GTV-MRI (r=0.851, p<0.05). CONCLUSION: With the database used, there is good agreement among observers. Hybrid PET/MRI in colorectal liver metastases radiotherapy may affect the GTV delineation. Moreover, the overlap degree between GTV-MRI and GTV-PET/MRI is higher and increases with volume.

18F-FACBC PET/MRI in the evaluation of human brain metastases: a case report.

BACKGROUND: Patients with metastatic cancer to the brain have a poor prognosis. In clinical practice, MRI is used to delineate, diagnose and plan treatment of brain metastases. However, MRI alone is limited in detecting micro-metastases, delineating lesions and discriminating progression from pseudo-progression. Combined PET/MRI utilises superior soft tissue images from MRI and metabolic data from PET to evaluate tumour structure and function. The amino acid PET tracer 18F-FACBC has shown promising results in discriminating high- and low-grade gliomas, but there are currently no reports on its use on brain metastases. This is the first study to evaluate the use of 18F-FACBC on brain metastases. CASE PRESENTATION: A middle-aged female patient with brain metastases was evaluated using hybrid PET/MRI with 18F-FACBC before and after stereotactic radiotherapy, and at suspicion of recurrence. Static/dynamic PET and contrast-enhanced T1 MRI data were acquired and analysed. This case report includes the analysis of four 18F-FACBC PET/MRI examinations, investigating their utility in evaluating functional and structural metastasis properties. CONCLUSION: Analysis showed high tumour-to-background ratios in brain metastases compared to other amino acid PET tracers, including high uptake in a very small cerebellar metastasis, suggesting that 18F-FACBC PET can provide early detection of otherwise overlooked metastases. Further studies to determine a threshold for 18F-FACBC brain tumour boundaries and explore its utility in clinical practice should be performed.

Advanced imaging techniques for neuro-oncologic tumor diagnosis, with an emphasis on PET-MRI imaging of malignant brain tumors.

PURPOSE OF REVIEW: This review will explore the latest in advanced imaging techniques, with a focus on the complementary nature of multiparametric, multimodality imaging using magnetic resonance imaging (MRI) and positron emission tomography (PET). RECENT FINDINGS: Advanced MRI techniques including perfusion-weighted imaging (PWI), MR spectroscopy (MRS), diffusion-weighted imaging (DWI), and MR chemical exchange saturation transfer (CEST) offer significant advantages over conventional MR imaging when evaluating tumor extent, predicting grade, and assessing treatment response. PET performed in addition to advanced MRI provides complementary information regarding tumor metabolic properties, particularly when performed simultaneously. 18F-fluoroethyltyrosine (FET) PET improves the specificity of tumor diagnosis and evaluation of post-treatment changes. Incorporation of radiogenomics and machine learning methods further improve advanced imaging. The complementary nature of combining advanced imaging techniques across modalities for brain tumor imaging and incorporating technologies such as radiogenomics has the potential to reshape the landscape in neuro-oncology.

Efficacy of delayed 18F-FDG hybrid PET/MRI for epileptic focus identification: a prospective cohort study.

OBJECTIVE: We sought to investigate the contribution of delayed 18F-FDG imaging data to epileptogenic zone (EZ) identification using a hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) system. METHODS: Forty-one patients with epilepsy underwent a brain dual time point 18F-FDG PET/MRI examination. All early imaging was acquired at approximately 40 min. Late imaging was classified as short delay (150.1 ± 20.2 min) or long delay (247.8 ± 24.6 min). Visual evaluation and scoring of 18F-FDG uptake at dual time points were performed. An SUVmean asymmetry index (AI) was calculated representing the difference in uptake between the EZ and the contralateral side. The EZ location was defined by a multidisciplinary team based on findings on video electroencephalography, 18F-FDG, and MRI. EZ location was classified as extratemporal lobe epilepsy (extra-TLE) or temporal lobe epilepsy (TLE). MRI findings were classified as positive if there were signal/structural abnormalities, or negative. AI of dual time points was compared between MRI-positive and MRI-negative, between extra-TLE and TLE, and between short delay and long delay of the late imaging time point. RESULTS: The AI at the delayed time points was increased by a mean of 3.7 over the early time point in all patients (P < 0.01). The biggest AIs were found in the MRI-positive group. The ΔAI between two imaging points were 3.71 ± 3.50 and 4.67 ± 7.94 for MRI-positive and MRI-negative; 4.52 ± 6.70 and 2.51 ± 2.42 for extra-TLE and TLE; and 4.24 ± 6.52 and 3.46 ± 2.90 for short delay and long delay groups, respectively. There were more patients with increased AI at the delayed time with MRI-positive (95.8%, 23/24), with extra-TLE (96.8%, 30/31), and with short delay time (93.7%, 30/32). Two observers who had no knowledge of the images chose 85.4% and 82.9% of the delay-time point images as the more obvious asymmetry from all images. The kappa value between the two observers was 0.66 with good agreement. CONCLUSION: Delayed 18F-FDG PET imaging can be used to better identify EZs with relatively greater metabolic asymmetry between the EZ and contralateral regions.

Utility of hybrid PET/MRI multiparametric imaging in navigating SEEG placement in refractory epilepsy.

PURPOSE: Stereo-electroencephalography (SEEG) implantation before epilepsy surgery is critical for precise localization and complete resection of the seizure onset zone (SOZ). Combined metabolic and morphological imaging using hybrid PET/MRI may provide supportive information for the optimization of the SEEG coverage of brain structures. In this study, we originally imported PET/MRI images into the SEEG positioning system to evaluate the application of PET/MRI in guiding SEEG implantation in refractory epilepsy patients. MATERIALS: Forty-two patients undergoing simultaneous PET/MRI examinations were recruited. All the patients underwent SEEG implantation guided by hybrid PET/MRI and surgical resection or ablation of epileptic lesion. Surgery outcome was assessed using a modified Engel classification one year (13.60 ± 2.49 months) after surgery. Areas of SOZ were identified using hybrid PET/MRI and concordance with SEEG was evaluated. Logistic regression analysis was used to predict the presence of a favorable outcome with the coherence of concordance of PET/MRI and SEEG. RESULTS: Hybrid PET/MRI (including visual PET, MRI, plus MI Neuro) identified SOZ lesions in 38 epilepsy patients (90.47 %). PET/MRI showed the same SOZ localization with SEEG in 29 patients (69.05 %), which was considered to be concordant. The concordance between the PET/MRI and SEEG findings was significantly predictive of a successful surgery outcome (odds ratio = 20.41; 95 % CI = 2.75-151.4, P = 0.003**). CONCLUSION: Hybrid PET/MRI combined visual PET, multiple sequences MRI and SPM PET helps identify epilepsy lesions particularly in subtle hypometabolic areas. Patients with concordant epileptic lesion localization on PET/MRI and SEEG demonstrated a more favorable outcome than those with inconsistent localization between modalities.

Multiparametric imaging hippocampal neurodegeneration and functional connectivity with simultaneous PET/MRI in Alzheimer's disease.

PURPOSE: The objective of this study is to investigate the hippocampal neurodegeneration and its associated aberrant functions in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients using simultaneous PET/MRI. METHODS: Forty-two cognitively normal controls (NC), 38 MCI, and 22 AD patients were enrolled in this study. All subjects underwent 18F-FDG PET/functional MRI (fMRI) and high-resolution T1-weighted MRI scans on a hybrid GE Signa PET/MRI scanner. Neurodegeneration in hippocampus and its subregions was quantified by regional gray matter volume and 18F-FDG standardized uptake value ratio (SUVR) relative to cerebellum. An iterative reblurred Van Cittert iteration method was used for voxelwise partial volume correction on 18F-FDG PET images. Regional gray matter volume was estimated from voxel-based morphometric analysis with MRI. fMRI data were analyzed after slice time correction and head motion correction using statistical parametric mapping (SPM12) with DPARSF toolbox. The regions of interest including hippocampus, cornu ammonis (CA1), CA2/3/dentate gyrus (DG), and subiculum were defined in the standard MNI space. RESULTS: Patient groups had reduced SUVR, gray matter volume, and functional connectivity compared to NC in CA1, CA2/3/DG, and subiculum (AD < MCI < NC). There was a linear correlation between the left CA2/3DG gray matter volume and 18F-FDG SUVR in AD patients (P < 0.001, r = 0.737). Significant correlation was also found between left CA2/3/DG-superior medial frontal gyrus functional connectivity and left CA2/3/DG hypometabolism in patients with AD. The functional connectivity of right CA1-precuneus in patients with MCI and right subiculum-superior frontal gyrus in patients with AD was positively correlated with mini mental status examination scores (P < 0.05). CONCLUSION: Our findings demonstrate that the associations existed at subregional hippocampal level between the functional connectivity measured by fMRI and neurodegeneration measured by structural MRI and 18F-FDG PET. Our results may provide a basis for precision neuroimaging of hippocampus in AD.

Multiresolution spatiotemporal mechanical model of the heart as a prior to constrain the solution for 4D models of the heart.

In several nuclear cardiac imaging applications (SPECT and PET), images are formed by reconstructing tomographic data using an iterative reconstruction algorithm with corrections for physical factors involved in the imaging detection process and with corrections for cardiac and respiratory motion. The physical factors are modeled as coefficients in the matrix of a system of linear equations and include attenuation, scatter, and spatially varying geometric response. The solution to the tomographic problem involves solving the inverse of this system matrix. This requires the design of an iterative reconstruction algorithm with a statistical model that best fits the data acquisition. The most appropriate model is based on a Poisson distribution. Using Bayes Theorem, an iterative reconstruction algorithm is designed to determine the maximum a posteriori estimate of the reconstructed image with constraints that maximizes the Bayesian likelihood function for the Poisson statistical model. The a priori distribution is formulated as the joint entropy (JE) to measure the similarity between the gated cardiac PET image and the cardiac MRI cine image modeled as a FE mechanical model. The developed algorithm shows the potential of using a FE mechanical model of the heart derived from a cardiac MRI cine scan to constrain solutions of gated cardiac PET images.

Recurrent prostate cancer after radical prostatectomy: restaging performance of 18F-choline hybrid PET/MRI.

To evaluate the diagnostic performance of a whole-body 18F-choline (FCH) hybrid PET/MRI for prostate cancer patients at biochemical relapse after radical prostatectomy (RP) compared to pelvic multiparametric MRI (mpMRI), one of the standard imaging modality for this patient population. From 2010 to 2016, 58 whole-body FCH PET/MRI studies with mpMRI acquisitions were performed in 53 prostate cancer patients relapsing after curative RP. Median PSA and PSA doubling time (PSA DT) at PET study were 1.5 ng/ml and 6.5 months, respectively. The overall positivity rate of FCH PET/MRI was 58.6% (n = 34), dropping to 44% in patients with a PSA ≤ 2 ng/ml (n = 36). Median PSA values in positive and negative PET/MRI studies were 2.2 ng/ml and 0.8 ng/ml, respectively, with no differences in PSA DT (6.5 vs. 6.6 months). A PSA value ≥ 1.5 ng/ml was a significant predictor of positivity on PET/MRI studies. Compared to PET, mpMRI identified more local relapses (17 vs. 14, p = 0.453) while PET outperformed whole-body Dixon MRI for regional (16 vs. 9, p = 0.016) and distant (12 vs. 6, p = 0.031) metastases. Compared to pelvic mpMRI, the treatment approach turned out to be influenced more frequently using whole-body FCH hybrid PET/MRI studies (58.6% vs. 38%). In prostate cancer patients with biochemical recurrence after RP, whole-body FCH PET/MRI achieved a higher detection rate of nodal/distant metastases compared to pelvic mpMRI alone, increasing the change of treatment strategy by more than 20%.

Screening for Dementia Caused by Modifiable Lifestyle Choices Using Hybrid PET/MRI.

Significant advances in positron emission tomography (PET) and magnetic resonance imaging (MRI) brain imaging in the early detection of dementia indicate that hybrid PET/MRI would be an effective tool to screen for dementia in the population living with lifestyle risk factors. Here we investigate the associated costs and benefits along with the needed imaging infrastructure. A demographic analysis determined the prevalence of dementia and its incidence. The expected value of the screening program was calculated assuming a sensitivity and specificity of 0.9, a prevalence of 0.1, a QALY factor of 0.348, a willingness to pay $114,000 CAD and the cost per PET/MRI scan of $2,000 CAD. It was assumed that each head PET/MRI could screen 3,000 individuals per year. The prevalence of dementia is increasing by almost two-fold every 20 years due to the increased population at ages where dementia is more prevalent. It has been shown that a five-year delay in the incidence of dementia would decrease the prevalence by some 45%. In Canada, a five-year delay corresponds to a health care savings of $27,000 CAD per subject per year. The expected value for screening was estimated at $23,745 CAD. The number of subjects to be screened per year in Canada, USA, and China between 60 and 79 was 11,405,000. The corresponding number of head-only hybrid PET/MRI systems needed is 3,800. A brain PET/MRI screening program is financially justifiable with respect to health care costs and justifies the continuing development of MRI compatible brain PET technology.

Combined Amino Acid Positron Emission Tomography and Advanced Magnetic Resonance Imaging in Glioma Patients.

Imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) provide valuable information about brain tumor patients. Particularly amino acid PET, advanced MRI techniques, and combinations thereof are of great interest for the non-invasive assessment of biological characteristics in patients with primary or secondary brain cancer. A methodological innovation that potentially advances research in patients with brain tumors is the increasing availability of hybrid PET/MRI systems, which enables the simultaneous acquisition of both imaging modalities. Furthermore, the advent of ultra-high field MRI scanners operating at magnetic field strengths of 7 T or more will allow further development of metabolic MR imaging at higher resolution. This review focuses on the combination of amino acid PET with MR spectroscopic imaging, perfusion- and diffusion-weighted imaging, as well as chemical exchange saturation transfer in patients with high-grade gliomas, especially glioblastomas.