Simultaneous Positron Emission Tomography Research Articles

Simultaneous Positron Emission Tomography and Molecular Magnetic Resonance Imaging of Cardiopulmonary Fibrosis in a Mouse Model of Left Ventricular Dysfunction.

Aging-associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)-magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model. Left ventricular dysfunction was induced by transverse aortic constriction (TAC) in 6-month-old senescence-accelerated prone mice, a subset of mice that received sham surgery. Three weeks after surgery, mice underwent simultaneous PET-MRI at 4.7 T. Collagen-targeted PET and fibrogenesis magnetic resonance (MR) probes were intravenously administered. PET signal was computed as myocardium- or lung-to-muscle ratio. Percent signal intensity increase and Δ lung-to-muscle ratio were computed from the pre-/postinjection magnetic resonance images. Elevated allysine in the heart (P=0.02) and lungs (P=0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase (P<0.0001) and Δlung-to-muscle ratio (P<0.0001). Hydroxyproline in the heart (P<0.0001) and lungs (P<0.01) were elevated in TAC mice, which corresponded to an increase in heart (myocardium-to-muscle ratio, P=0.02) and lung (lung-to-muscle ratio, P<0.001) PET measurements. Pressure-volume loop and echocardiography demonstrated adverse left ventricular remodeling, function, and increased right ventricular systolic pressure in TAC mice. Administration of collagen-targeted PET and allysine-targeted MR probes led to elevated PET-magnetic resonance imaging signals in the myocardium and lungs of TAC mice. The study demonstrates the potential to detect fibrosis and fibrogenesis in cardiopulmonary disease through a dual molecular PET-magnetic resonance imaging protocol.

Signal separation of simultaneous dual-tracer PET imaging based on global spatial information and channel attention

BackgroundSimultaneous dual-tracer positron emission tomography (PET) imaging efficiently provides more complete information for disease diagnosis. The signal separation has long been a challenge of dual-tracer PET imaging. To predict the single-tracer images, we proposed a separation network based on global spatial information and channel attention, and connected it to FBP-Net to form the FBPnet-Sep model.ResultsExperiments using simulated dynamic PET data were conducted to: (1) compare the proposed FBPnet-Sep model to Sep-FBPnet model and currently existing Multi-task CNN, (2) verify the effectiveness of modules incorporated in FBPnet-Sep model, (3) investigate the generalization of FBPnet-Sep model to low-dose data, and (4) investigate the application of FBPnet-Sep model to multiple tracer combinations with decay corrections. Compared to the Sep-FBPnet model and Multi-task CNN, the FBPnet-Sep model reconstructed single-tracer images with higher structural similarity, peak signal-to-noise ratio and lower mean squared error, and reconstructed time-activity curves with lower bias and variation in most regions. Excluding the Inception or channel attention module resulted in degraded image qualities. The FBPnet-Sep model showed acceptable performance when applied to low-dose data. Additionally, it could deal with multiple tracer combinations. The qualities of predicted images, as well as the accuracy of derived time-activity curves and macro-parameters were slightly improved by incorporating a decay correction module.ConclusionsThe proposed FBPnet-Sep model was considered a potential method for the reconstruction and signal separation of simultaneous dual-tracer PET imaging.

Investigating the relationship between hippocampus/dentate gyrus volume and hypothalamus metabolism in participants with major depressive disorder

Reduced hippocampal volume occurs in major depressive disorder (MDD), potentially due to elevated glucocorticoids from an overactivated hypothalamus–pituitary–adrenal (HPA) axis. To examine this in humans, hippocampal volume and hypothalamus (HPA axis) metabolism was quantified in participants with MDD before and after antidepressant treatment. 65 participants (n = 24 males, n = 41 females) with MDD were treated in a double-blind, randomized clinical trial of escitalopram. Participants received simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) before and after treatment. Linear mixed models examined the relationship between hippocampus/dentate gyrus volume and hypothalamus metabolism. Chi-squared tests and multivariable logistic regression examined the association between hippocampus/dentate gyrus volume change direction and hypothalamus activity change direction with treatment. Multiple linear regression compared these changes between remitter and non-remitter groups. Covariates included age, sex, and treatment type. No significant linear association was found between hippocampus/dentate gyrus volume and hypothalamus metabolism. 62% (38 of 61) of participants experienced a decrease in hypothalamus metabolism, 43% (27 of 63) of participants demonstrated an increase in hippocampus size (51% [32 of 63] for the dentate gyrus) following treatment. No significant association was found between change in hypothalamus activity and change in hippocampus/dentate gyrus volume, and this association did not vary by sex, medication, or remission status. As this multimodal study, in a cohort of participants on standardized treatment, did not find an association between hypothalamus metabolism and hippocampal volume, it supports a more complex pathway between hippocampus neurogenesis and hypothalamus metabolism changes in response to treatment.

Teaching a hands-on session on simultaneous Positron Emission Tomography and Magnetic Resonance image acquisition and quantification in a clinical setting

Positron Emission Tomography/Magnetic Resonance (PET/MR) imaging, is a novel imaging modality that combines the capabilities of two powerful imaging techniques in a single acquisition. This unique integration allows for simultaneous acquisition of both metabolic and structural data within a single imaging session. In this sense, PET/MR offers a comprehensive and innovative approach to medical imaging, but accompanied by its intrinsic physics and engineering complexity, involving intricate synchronization of high-performance detectors, electromagnetic shielding, and sophisticated correction algorithms, among others. In this hands-on session performed during the 6th INFIERI summer school (Madrid, Spain), we described an introduction to simultaneous PET/MR image acquisition and quantification in a real clinical to students from diverse backgrounds in physics and engineering. We first presented the fundamental aspects of PET/MR image acquisition, including the main theoretical characteristics of PET/MR physics and electronics, visiting the PET/MR facilities at Hospital Universitario HM Puerta del Sur (HM Hospitales, Móstoles, Madrid), and discussing the main PET/MR clinical and research applications. Then, we followed with a practical session on PET/MR image quantification, preparing the students to understand and solve examples on image reconstruction, multimodal data visualization, inhomogeneity correction, image registration, and attenuation correction exploiting the simplicity and usefulness of 3D Slicer.

Simultaneous 18-FDG PET and MR imaging in lower extremity arterial disease.

Simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) is a novel hybrid imaging method integrating the advances of morphological tissue characterization of MRI with the pathophysiological insights of PET applications. This study evaluated the use of simultaneous 18-FDG PET/MR imaging for characterizing atherosclerotic lesions in lower extremity arterial disease (LEAD). Eight patients with symptomatic stenoses of the superficial femoral artery (SFA) under simultaneous acquisition of 18-FDG PET and contrast-enhanced MRI using an integrated whole-body PET/MRI scanner. Invasive plaque characterization of the SFA was performed by intravascular imaging using optical coherence tomography. Histological analysis of plaque specimens was performed after directional atherectomy. MRI showed contrast enhancement at the site of arterial stenosis, as assessed on T2-w and T1-w images, compared to a control area of the contralateral SFA (0.38 ± 0.15 cm vs. 0.23 ± 0.11 cm; 1.77 ± 0.19 vs. 1.57 ± 0.15; p-value <0.05). On PET imaging, uptake of 18F-FDG (target-to-background ratio TBR > 1) at the level of symptomatic stenosis was observed in all but one patient. Contrast medium-induced MR signal enhancement was detected in all plaques, whereas FDG uptake in PET imaging was increased in lesions with active fibroatheroma and reduced in fibrocalcified lesions. In this multimodal imaging study, we report the feasibility and challenges of simultaneous PET/MR imaging of LEAD, which might offer new perspectives for risk estimation.

Recent advances in combined Positron Emission Tomography and Magnetic Resonance Imaging

Abstract Hybrid imaging modalities combine two or more medical imaging techniques offering exciting new possibilities to image the structure, function and biochemistry of the human body in far greater detail than has previously been possible to improve patient diagnosis. In this context, simultaneous Positron Emission Tomography and Magnetic Resonance (PET/MR) imaging offers great complementary information, but it also poses challenges from the point of view of hardware and software compatibility. The PET signal may interfere with the MR magnetic field and vice-versa, posing several challenges and constrains in the PET instrumentation for PET/MR systems. Additionally, anatomical maps are needed to properly apply attenuation and scatter corrections to the resulting reconstructed PET images, as well motion estimates to minimize the effects of movement throughout the acquisition. In this review, we summarize the instrumentation implemented in modern PET scanners to overcome these limitations, describing the historical development of hybrid PET/MR scanners. We pay special attention to the methods used in PET to achieve attenuation, scatter and motion correction when it is combined with MR, and how both imaging modalities may be combined in PET image reconstruction algorithms.

Evaluation of the MRI compatibility of PET detectors modules for organ-specific inserts in a 3T and 7T MRI scanner.

Simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) scanners and inserts are valuable tools for accurate diagnosis, treatment planning, and monitoring due to their complementary information. However, the integration of a PET system into an MRI scanner presents technical challenges for a distortion-free operation. We aim to develop a PET insert dedicated to breast imaging in combination with the 3T PET/MRI scanner Biograph mMR (Siemens Healthineers) as well as a brain PET insert for the 7T MRI scanner MAGNETOM Terra (Siemens Healthineers). For this development, we selected as a basis the C13500 series PET modules (Hamamatsu Photonics K.K.) as they offer an all-in-one solution with a scalable, modular design for compact integration with state-of-the-art performance. The original PET modules were not designed to be operated with an MRI scanner, therefore we implemented several modifications such as signal transmission via plastic optical fiber, radio frequency (RF) shielding of the front-end electronics, and filter for the power supply lines. In this work, we evaluated the mutual MRI compatibility between the modified PET modules and the 3T and 7T MRI scanner. We used a proof-of-concept setup with two detectors to comprehensively evaluate a potential distortion of the performance of the modified PET modules whilst exposing them to a variety of MR sequences up to the peak operation conditions of the Biograph mMR. A method using the periodicity of the sequences to identify distortions of the PET events in the phase of RF pulse transmission was introduced. Vice versa, the potential distortion of the Biograph mMR was evaluated by vendor proprietary MRI compatibility test sequences. Afterwards, these studies were extended to the MAGNETOM Terra. No distortions were introduced by gradient field switching (field strength up to 20 mT/m at a slew rate of 66.0 T/ms-1 ). However, RF pulse transmission induced a reduction of the single event rate from 33.0 kcounts/s to 32.0 kcounts/s and a degradation of the coincidence resolution time from 251 to 299ps. Further, the proposed method revealed artifacts in the energy and timing histograms. Finally, by using the front-end filters it was possible to prevent any RF pulse induced distortion of event rate, energy, or time stamps even for a 700° flip angle (45.5 μT) sequence. The evaluations to assess potential distortions of the MRI scanner showed that carefully designed RF shielding boxes for the PET modules were required to prevent distortion of the RF spectra. The increase in B0 field inhomogeneity of 0.254ppm and local changes of the B1 field of 12.5% introduced by the PET modules did not qualitatively affect the MR imaging with a spin echo and MPRAGE sequence for the Biograph mMR and the MAGNETOM Terra, respectively. Our study demonstrates the feasibility of using a modified version of the PET modules in combination with 3T and 7T MRI scanners. Building upon the encouraging MRI compatibility results from our proof-of-concept detectors, we will proceed to develop PET inserts for breast and brain imaging using these modules.

Cerebral hypometabolism mediates the effect of stroke volume on cognitive impairment in heart failure patients.

The present study aimed to phenotype the cerebral structural and glucose metabolic alterations in patients with heart failure (HF) using simultaneous positron emission tomography (PET)/magnetic resonance (MR) and to investigate their relationship to cardiac biomarkers and cognitive performance. Forty-two HF patients caused by ischaemic heart disease (mean age 67.2±10.4, 32 males) and 32 age- and sex-matched healthy volunteers (mean age 61.3±4.8, 18 males) were included in this study. Participants underwent simultaneous cerebral fluorine-18 (18 F) fluorodeoxyglucose PET/MR followed by cardiac MR scan, and neuropsychological scores were obtained to assess cognitive performance. The grey matter volume (GMV) and standardized uptake value ratio (SUVR) were calculated to examine cerebral structural and metabolic alterations. Cardiac biomarkers included cardiac MR parameters and cardiac serum laboratory tests. Mediation analysis was performed to explore the associations among cerebral alterations, cardiac biomarkers, and cognitive performance. HF patients demonstrated notable cognitive impairment compared with normal controls (P<0.001). Furthermore, HF patients exhibited regional brain hypometabolism in the bilateral calcarine cortex, caudate nucleus, thalamus, hippocampus, precuneus, posterior cingulate cortex, lingual and olfactory cortex, and GMV reduction in bilateral thalamus and hippocampus (cluster level at P<0.05, Gaussian random field correction). The SUVR of the hypometabolic brain regions was correlated with the Montreal Cognitive Assessment (MoCA) scores (r=0.55, P = 0.038) and cardiac stroke volume (r=0.49, P=0.002). Cerebral hypometabolism played a key role in the relationship between the decreased stroke volume and MoCA scores, with a mediation effect of 33.2%. HF patients suffered cerebral metabolic and structural alterations in regions associated with cognition. The observed correlation between cardiac stroke volume and cognitive impairment underscored the potential influence of cerebral hypometabolism, suggesting that cerebral hypometabolism due to chronic systemic hypoperfusion may significantly contribute to cognitive impairment in HF patients.

Multiparametric hippocampal signatures for early diagnosis of Alzheimer's disease using 18F-FDG PET/MRI Radiomics.

This study aimed to explore the utility of hippocampal radiomics using multiparametric simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) for early diagnosis of Alzheimer's disease (AD). A total of 53 healthy control (HC) participants, 55 patients with amnestic mild cognitive impairment (aMCI), and 51 patients with AD were included in this study. All participants accepted simultaneous PET/MRI scans, including 18F-fluorodeoxyglucose (18F-FDG) PET, 3D arterial spin labeling (ASL), and high-resolution T1-weighted imaging (3D T1WI). Radiomics features were extracted from the hippocampus region on those three modal images. Logistic regression models were trained to classify AD and HC, AD and aMCI, aMCI and HC respectively. The diagnostic performance and radiomics score (Rad-Score) of logistic regression models were evaluated from 5-fold cross-validation. The hippocampal radiomics features demonstrated favorable diagnostic performance, with the multimodal classifier outperforming the single-modal classifier in the binary classification of HC, aMCI, and AD. Using the multimodal classifier, we achieved an area under the receiver operating characteristic curve (AUC) of 0.98 and accuracy of 96.7% for classifying AD from HC, and an AUC of 0.86 and accuracy of 80.6% for classifying aMCI from HC. The value of Rad-Score differed significantly between the AD and HC (p < 0.001), aMCI and HC (p < 0.001) groups. Decision curve analysis showed superior clinical benefits of multimodal classifiers compared to neuropsychological tests. Multiparametric hippocampal radiomics using PET/MRI aids in the identification of early AD, and may provide a potential biomarker for clinical applications.

The PREMISE database of 20 Macaca fascicularis PET/MRI brain images available for research

Non-human primate studies are unique in translational research, especially in neurosciences where neuroimaging approaches are the preferred methods used for cross-species comparative neurosciences. In this regard, neuroimaging database development and sharing are encouraged to increase the number of subjects available to the community, while limiting the number of animals used in research. Here we present a simultaneous positron emission tomography (PET)/magnetic resonance (MR) dataset of 20 Macaca fascicularis images structured according to the Brain Imaging Data Structure standards. This database contains multiple MR imaging sequences (anatomical, diffusion and perfusion imaging notably), as well as PET perfusion and inflammation imaging using respectively [15O]H2O and [11C]PK11195 radiotracers. We describe the pipeline method to assemble baseline data from various cohorts and qualitatively assess all the data using signal-to-noise and contrast-to-noise ratios as well as the median of intensity and the pseudo-noise-equivalent-count rate (dynamic and at maximum) for PET data. Our study provides a detailed example for quality control integration in preclinical and translational PET/MR studies with the aim of increasing reproducibility. The PREMISE database is stored and available through the PRIME-DE consortium repository.

Tumour status prediction by means of carbon-ion beam irradiation: comparison of washout rates between in-beam PET and DCE-MRI in rats

Objective. Tumour response to radiation therapy appears as changes in tumour vascular condition. There are several methods for analysing tumour blood circulatory changes one of which is dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), but there is no method that can observe the tumour vascular condition and physiological changes at the site of radiation therapy. Positron emission tomography (PET) has been applied for treatment verification in charged particle therapy, which is based on the detection of positron emitters produced through nuclear fragmentation reactions in a patient’s body. However, the produced positron emitters are washed out biologically depending on the tumour vascular condition. This means that measuring the biological washout rate may allow evaluation of the tumour radiation response, in a similar manner to DCE-MRI. Therefore, this study compared the washout rates in rats between in-beam PET during 12C ion beam irradiation and DCE-MRI. Approach. Different vascular conditions of the tumour model were prepared for six nude rats. The tumour of each nude rat was irradiated by a 12C ion beam with simultaneous in-beam PET measurement. In 10–12 h, the DCE-MRI experiment was performed for the same six nude rats. The biological washout rate of the produced positron emitters (k 2,1st) and the MRI contrast agent (k 2a) were derived using the single tissue compartment model. Main results. A linear correlation was observed between k 2,1st and k 2a, and they were inversely related to fractional necrotic volume. Significance. This is the first animal study which confirmed the biological washout rate of in-beam PET correlates closely with tumour vascular condition measured with the MRI contrast agent administrated intravenously.

3D-printed dual holder system for simultaneous rat PET scanning: design and influence on quantification

BackgroundThe low throughout of small animal positron emission tomography (PET) images acquisitions represents a substantial limitation. The aims of this study were (i) to design a low-cost support for simultaneous dynamic PET scanning of two lying rats and (ii) to study its impact on brain image quantification.ResultsAccuracy of concentration measurement was 5.5% for one phantom in the field of view, and 5.7% for two phantoms measured simultaneously. Ratio concentration between phantoms showed an error of 6.7% ± 5.1% for Solo upper position, 6.7% ± 3.7% for Solo lower position, 5.9% ± 4.3% for Duo upper position, and 7.4% ± 6% for Duo lower position 6.7% for separated measures, and 6.6% for simultaneous measures.In vivo distribution profiles showed no difference between solo and duo uptakes. Region of Interest quantification in the whole brain showed 4.4% variability solo and 3.5% duo. The quantified test–retest bias was 8% in solo and 5% in duo, and the Intraclass Correlation Coefficient was comparable in solo and duo (0.969 vs. 0.966).ConclusionsOur results showed that simultaneous scans of two rats in INVEON do not affect quantification. The dual support system will allow us to reduce protocol costs and duration.

Deep learning-enabled quantification of simultaneous PET/MRI for cell transplantation monitoring

Current methods of invivo imaging islet cell transplants for diabetes using magnetic resonance imaging (MRI) are limited by their low sensitivity. Simultaneous positron emission tomography (PET)/MRI has greater sensitivity and ability to visualize cell metabolism. However, this dual-modality tool currently faces two major challenges for monitoring cells. Primarily, the dynamic conditions of PET such as signal decay and spatiotemporal change in radioactivity prevent accurate quantification of the transplanted cell number. In addition, selection bias from different radiologists renders human error in segmentation. This calls for the development of artificial intelligence algorithms for the automated analysis of PET/MRI of cell transplantations. Here, we combined K-means++ for segmentation with a convolutional neural network to predict radioactivity in cell-transplanted mouse models. This study provides a tool combining machine learning with a deep learning algorithm for monitoring islet cell transplantation through PET/MRI. It also unlocks a dynamic approach to automated segmentation and quantification of radioactivity in PET/MRI.

Striatal dopamine in anhedonia: A simultaneous [11C]raclopride positron emission tomography and functional magnetic resonance imaging investigation

BackgroundAnhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample. MethodsParticipants with (n = 25) and without (n = 12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [11C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors. ResultsRelative to controls, the anhedonia group exhibited decreased task-related DA release in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC. ConclusionsResults provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia.

Imaging regional histone deacetylase expression in dementia with Lewy bodies with [11C]Martinostat (P13-6.008)

<h3>Objective:</h3> To image brain histone deacetylase (HDAC) expression using [¹¹C]Martinostat positron emission tomography (PET) in living participants with dementia with Lewy bodies (DLB). <h3>Background:</h3> Epigenetic modifications via HDACs and other mechanisms regulate transcription of specific genes in response to a cell’s environment or exposure, and epigenetic changes have been observed in postmortem brain tissue in Lewy body diseases. However, whether HDAC changes arise early in disease or only as a late phenomenon, and whether regional brain HDAC expression relates to the clinical or pathologic features of the disease remain uncertain. <h3>Design/Methods:</h3> Seven subjects with DLB and 17 age-matched healthy control (HC) subjects provided informed consent to participate. Participants underwent cognitive, motor, and neuropsychiatric evaluation followed by simultaneous MR and PET imaging with [¹¹C]Martinostat, a radioligand developed at the Massachusetts General Hospital (MGH) Martinos Center for Biomedical Imaging that binds class I HDACs with high affinity and selectivity. Data were reconstructed and standardized uptake value ratios computed using a global reference. A whole-brain voxelwise analysis was followed by region of interest-based analysis. <h3>Results:</h3> Compared to HC subjects, [¹¹C]Martinostat uptake in DLB was increased in regions enriched for Lewy body pathology, including the brainstem, medial temporal lobe, and anterior cingulate. Increased uptake was also observed in regions associated with motor function, including the striatum, motor cortex, and cerebellum. [¹¹C]Martinostat uptake was decreased in parietal cortex. <h3>Conclusions:</h3> These preliminary findings in living participants with DLB identify abnormal class I HDAC expression in regions associated with Lewy body pathology, motor circuitry, and cognition. They set the stage for planned comparisons with antemortem Parkinson’s disease (PD) and with postmortem regional HDAC expression in PD and DLB. <b>Disclosure:</b> The institution of Dr. Goodheart has received research support from American Academy of Neurology. Mr. Yoo has nothing to disclose. Ms. Striar has nothing to disclose. Ms. Quan has nothing to disclose. Prof. Wey has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Gomperts has received personal compensation in the range of $0-$499 for serving as a Consultant for EIP. Dr. Gomperts has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Jannsen. The institution of Dr. Gomperts has received research support from NIH. The institution of Dr. Gomperts has received research support from LBDA. The institution of Dr. Gomperts has received research support from DOD/CDMRP. The institution of Dr. Gomperts has received research support from FFFPRI. The institution of Dr. Gomperts has received research support from NIH. The institution of Dr. Gomperts has received research support from MJFF. The institution of Dr. Gomperts has received research support from NIH. The institution of Dr. Gomperts has received research support from NIH. The institution of Dr. Gomperts has received research support from MJFF. The institution of Dr. Gomperts has received research support from NIH. The institution of Dr. Gomperts has received research support from NIH.

Combined In Vivo Microdialysis and PET Studies to Validate [11C]Yohimbine Binding as a Marker of Noradrenaline Release.

The noradrenaline system attracts attention for its role in mood disorders and neurodegenerative diseases but the lack of well-validated methods impairs our understanding when assessing its function and release in vivo. This study combines simultaneous positron emission tomography (PET) and microdialysis to explore if [11C]yohimbine, a selective antagonist radioligand of the α2 adrenoceptors, may be used to assess in vivo changes in synaptic noradrenaline during acute pharmacological challenges. Anesthetised Göttingen minipigs were positioned in a head holder in a PET/CT device. Microdialysis probes were placed in the thalamus, striatum and cortex and dialysis samples were collected every 10 min. Three 90 min [11C]yohimbine scans were acquired: at baseline and at two timepoints after the administration of amphetamine (1-10 mg/kg), a non-specific releaser of dopamine and noradrenaline, or nisoxetine (1 mg/kg), a specific noradrenaline transporter inhibitor. [11C]yohimbine volumes of distribution (VT) were obtained using the Logan kinetic model. Both challenges induced a significant decrease in yohimbine VT, with time courses reflecting their different mechanisms of action. Dialysis samples revealed a significant increase in noradrenaline extracellular concentrations after challenge and an inverse correlation with changes in yohimbine VT. These data suggest that [11C]yohimbine can be used to evaluate acute variations in synaptic noradrenaline concentrations after pharmacological challenges.

Direct reconstruction for simultaneous dual-tracer PET imaging based on multi-task learning

BackgroundSimultaneous dual-tracer positron emission tomography (PET) imaging can observe two molecular targets in a single scan, which is conducive to disease diagnosis and tracking. Since the signals emitted by different tracers are the same, it is crucial to separate each single tracer from the mixed signals. The current study proposed a novel deep learning-based method to reconstruct single-tracer activity distributions from the dual-tracer sinogram.MethodsWe proposed the Multi-task CNN, a three-dimensional convolutional neural network (CNN) based on a framework of multi-task learning. One common encoder extracted features from the dual-tracer dynamic sinogram, followed by two distinct and parallel decoders which reconstructed the single-tracer dynamic images of two tracers separately. The model was evaluated by mean squared error (MSE), multiscale structural similarity (MS-SSIM) index and peak signal-to-noise ratio (PSNR) on simulated data and real animal data, and compared to the filtered back-projection method based on deep learning (FBP-CNN).ResultsIn the simulation experiments, the Multi-task CNN reconstructed single-tracer images with lower MSE, higher MS-SSIM and PSNR than FBP-CNN, and was more robust to the changes in individual difference, tracer combination and scanning protocol. In the experiment of rats with an orthotopic xenograft glioma model, the Multi-task CNN reconstructions also showed higher qualities than FBP-CNN reconstructions.ConclusionsThe proposed Multi-task CNN could effectively reconstruct the dynamic activity images of two single tracers from the dual-tracer dynamic sinogram, which was potential in the direct reconstruction for real simultaneous dual-tracer PET imaging data in future.

Sequential and Hybrid PET/MRI Acquisition in Follow-Up Examination of Glioblastoma Show Similar Diagnostic Performance.

Both positron emission tomography (PET) and magnetic resonance imaging (MRI), including dynamic susceptibility contrast perfusion (DSC-PWI), are crucial for treatment monitoring of patients with high-grade gliomas. In clinical practice, they are usually conducted at separate time points. Whether this affects their diagnostic performance is presently unclear. To this end, we retrospectively reviewed 38 patients with pathologically confirmed glioblastoma (IDH wild-type) and suspected tumor recurrence after radiotherapy. Only patients who received both a PET−MRI (where DSC perfusion was acquired simultaneously with a FET-PET) and a separate MRI exam (including DSC perfusion) were included. Tumors were automatically segmented into contrast-enhancing tumor (CET), necrosis, and edema. To compare the simultaneous as well as the sequential DSC perfusion to the FET-PET, we calculated Dice overlap, global mutual information as well as voxel-wise Spearman correlation of hotspot areas. For the joint assessment of PET and MRI, we computed logistic regression models for the differentiation between true progression (PD) and treatment-related changes (TRC) using simultaneously or sequentially acquired images as input data. We observed no significant differences between Dice overlap (p = 0.17; paired t-test), mutual information (p = 0.18; paired t-test) and Spearman correlation (p = 0.90; paired t-test) when comparing simultaneous PET−MRI and sequential PET/MRI acquisition. This also held true for the subgroup of patients with >14 days between exams. Importantly, for the diagnostic performance, ROC analysis showed similar AUCs for differentiation of PD and TRC (AUC simultaneous PET: 0.77; AUC sequential PET: 0.78; p = 0.83, DeLong’s test). We found no relevant differences between simultaneous and sequential acquisition of FET-PET and DSC perfusion, also regarding their diagnostic performance. Given the increasing attention to multi-parametric assessment of glioma treatment response, our results reassuringly suggest that sequential acquisition is clinically and scientifically acceptable.

PET-MRI of Coronary Artery Disease.

Simultaneous positron emission tomography and magnetic resonance imaging (PET-MRI) combines the anatomical detail and tissue characterization of MRI with the functional information from PET. Within the coronary arteries, this hybrid technique can be used to identify biological activity combined with anatomically high-risk plaque features to better understand the processes underlying coronary atherosclerosis. Furthermore, the downstream effects of coronary artery disease on the myocardium can be characterized by providing information on myocardial perfusion, viability, and function. This review will describe the current capabilities of PET-MRI in coronary artery disease and discuss the limitations and future directions of this emerging technique. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

Development of Compton-PET hybrid imaging system with CeBr3-SiPM arrays

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are both established imaging technologies in nuclear medicine that are clinically available. However, simultaneous PET and SPECT nuclide imaging is difficult to accomplish with current equipment because of their distinct principles. In light of this, we have developed and demonstrated a GAGG scintillator based Compton-PET hybrid imaging system capable of performing PET and Compton imaging simultaneously. Alternatively, the CeBr3 scintillator possesses more desirable properties, including a high light yield (>60000 photons/MeV), a fast decay time (∼19 ns), and an excellent energy resolution (<4%@662 keV). Herein, we developed an 8 × 8 array of CeBr3 detector based instrumentation by using 64 channel fast signal processing slew rate limited Time over Threshold (ToT) based application-specific integrated circuits and a field programmable gate array ToT data acquisition system with a 62.5 ps accuracy. Furthermore, we evaluated the system’s basic performances. The mean and greatest energy resolutions were 10.1% and 6.0% (FWHM) for 662 keV. The time resolution was 239 ps (FWHM) after offset calibration. We also achieved a proof-of-concept based on single source.