Whole-body Positron Emission Tomography Imaging Research Articles

Deep denoiser prior driven relaxed iterated Tikhonov method for low-count PET image restoration

Objective. Low-count positron emission tomography (PET) imaging is an efficient way to promote more widespread use of PET because of its short scan time and low injected activity. However, this often leads to low-quality PET images with clinical image reconstruction, due to high noise and blurring effects. Existing PET image restoration (IR) methods hinder their own restoration performance due to the semi-convergence property and the lack of suitable denoiser prior. Approach. To overcome these limitations, we propose a novel deep plug-and-play IR method called Deep denoiser Prior driven Relaxed Iterated Tikhonov method (DP-RI-Tikhonov). Specifically, we train a deep convolutional neural network denoiser to generate a flexible deep denoiser prior to handle high noise. Then, we plug the deep denoiser prior as a modular part into a novel iterative optimization algorithm to handle blurring effects and propose an adaptive parameter selection strategy for the iterative optimization algorithm. Main results. Simulation results show that the deep denoiser prior plays the role of reducing noise intensity, while the novel iterative optimization algorithm and adaptive parameter selection strategy can effectively eliminate the semi-convergence property. They enable DP-RI-Tikhonov to achieve an average quantitative result (normalized root mean square error, structural similarity) of (0.1364, 0.9574) at the stopping iteration, outperforming a conventional PET IR method with an average quantitative result of (0.1533, 0.9523) and a state-of-the-art deep plug-and-play IR method with an average quantitative result of (0.1404, 0.9554). Moreover, the advantage of DP-RI-Tikhonov becomes more obvious at the last iteration. Experiments on six clinical whole-body PET images further indicate that DP-RI-Tikhonov successfully reduces noise intensity and recovers fine details, recovering sharper and more uniform images than the comparison methods. Significance. DP-RI-Tikhonov’s ability to reduce noise intensity and effectively eliminate the semi-convergence property overcomes the limitations of existing methods. This advancement may have substantial implications for other medical IR.

Tissue-based T cell activation and viral RNA persist for up to 2 years after SARS-CoV-2 infection.

The mechanisms of postacute medical conditions and unexplained symptoms after SARS-CoV-2 infection [Long Covid (LC)] are incompletely understood. There is growing evidence that viral persistence, immune dysregulation, and T cell dysfunction may play major roles. We performed whole-body positron emission tomography imaging in a well-characterized cohort of 24 participants at time points ranging from 27 to 910 days after acute SARS-CoV-2 infection using the radiopharmaceutical agent [18F]F-AraG, a selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the postacute COVID-19 group, which included those with and without continuing symptoms, was higher compared with prepandemic controls in many regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. T cell activation in the spinal cord and gut wall was associated with the presence of LC symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms specifically. Increased T cell activation in these tissues was also observed in many individuals without LC. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization of SARS-CoV-2 RNA and immunohistochemical studies in a subset of five participants with LC symptoms. We identified intracellular SARS-CoV-2 single-stranded spike protein-encoding RNA in rectosigmoid lamina propria tissue in all five participants and double-stranded spike protein-encoding RNA in three participants up to 676 days after initial COVID-19, suggesting that tissue viral persistence could be associated with long-term immunologic perturbations.

Targeted protein degradation combined with PET imaging reveals the role of host PD-L1 in determining anti-PD-1 therapy efficacy.

Immunohistochemical staining of programmed death-ligand 1 (PD-L1) in tumor biopsies acquired through invasive procedures is routinely employed in clinical practice to identify patients who are most likely to benefit from anti-programmed cell death protein 1 (PD-1) therapy. Nevertheless, PD-L1 expression is observed in various cellular subsets within tumors and their microenvironments, including tumor cells, dendritic cells, and macrophages. The impact of PD-L1 expression across these different cell types on the responsiveness to anti-PD-1 treatment is yet to be fully understood. We synthesized polymer-based lysosome-targeting chimeras (LYTACs) that incorporate both PD-L1-targeting motifs and liver cell-specific asialoglycoprotein receptor (ASGPR) recognition elements. Small-animal positron emission tomography (PET) imaging of PD-L1 expression was also conducted using a PD-L1-specific radiotracer 89Zr-αPD-L1/Fab. The PD-L1 LYTAC platform was capable of specifically degrading PD-L1 expressed on liver cancer cells through the lysosomal degradation pathway via ASGPR without impacting the PD-L1 expression on host cells. When coupled with whole-body PD-L1 PET imaging, our studies revealed that host cell PD-L1, rather than tumor cell PD-L1, is pivotal in the antitumor response to anti-PD-1 therapy in a mouse model of liver cancer. The LYTAC strategy, enhanced by PET imaging, has the potential to surmount the limitations of knockout mouse models and to provide a versatile approach for the selective degradation of target proteins in vivo. This could significantly aid in the investigation of the roles and mechanisms of protein functions associated with specific cell subsets in living subjects.

Reduced count pediatric whole-body 18F-FDG PET imaging reconstruction with a Bayesian penalized likelihood algorithm.

Advanced positron emission tomography (PET) image reconstruction methods promise to allow optimized PET/CT protocols with improved image quality,decreased administered activity and/or acquisition times. To evaluate the impact of reducing counts(simulating reduced acquisition time) in block sequential regularized expectation maximization (BSREM) reconstructed pediatric whole-body 18F-fluorodeoxyglucose (FDG) PET images, and to compare BSERM with ordered-subset expectation maximization (OSEM) reconstructed reduced-count images. Twenty children (16 male) underwent clinical whole-body 18F-FDG PET/CT examinations using a 25-cm axial field-of-view (FOV) digital PET/CT system at 90s per bed (s/bed) with BSREM reconstruction (β=700). Reduced count simulations with varied BSREM β levels were generated from list-mode data: 60s/bed, β=800; 50s/bed, β=900; 40s/bed, β=1000; and 30s/bed, β=1300. In addition, a single OSEM reconstruction was created at 60s/bed based on prior literature. Qualitative (Likert scores) and quantitative (standardized uptake value [SUV]) analyses were performed to evaluate image quality and quantitation across simulated reconstructions. The mean patient age was 9.0 ± 5.5 (SD) years, mean weight was 38.5 ± 24.5kg, and mean administered 18F-FDG activity was 4.5 ± 0.7 (SD) MBq/kg. Between BSREM reconstructions, no qualitative measure showed a significant difference versus the 90s/bed β=700 standard (all P>0.05). SUVmax values for lesions were significantly lower from 90s/bed, β=700 only at a simulated acquisition time of 30s/bed, β=1300 (P=0.001). In a side-by-side comparison of BSREM versus OSEM reconstructions, 40s/bed, β=1000 images were generally preferred over 60s/bed TOF OSEM images. In children who undergo whole-body 18F-FDG PET/CT on a 25-cm FOV digital PET/CT scanner, reductions in acquisition time or, by corollary, administered radiopharmaceutical activity of >50% from a clinical standard of 90s/bed may be possible while maintaining diagnostic quality when a BSREM reconstruction algorithm is used.

Metabolic interactions between organs in overweight and obesity using total-body positron emission tomography.

Overweight and obesity is a complex condition resulting from unbalanced energy homeostasis among various organs. However, systemic abnormalities in overweight and obese people are seldom explored in vivo by metabolic imaging techniques. The aim of this study was to determine metabolic abnormities throughout the body in overweight and obese adults using total-body positron emission tomography (PET) glucose uptake imaging. Thirty normal weight subjects [body mass index (BMI) < 25 kg/m2, 55.47 ± 13.94 years, 16 men and 14 women], and 26 overweight and obese subjects [BMI ≥ 25 kg/m2, 52.38 ± 9.52 years, 21 men and 5 women] received whole-body 18F-fluorodeoxyglucose PET imaging using the uEXPLORER. Whole-body standardized uptake value normalized by lean body mass (SUL) images were calculated. Metabolic networks were constructed based on the whole-body SUL images using covariance network approach. Both group-level and individual-level network differences between normal weight and overweight/obese subjects were evaluated. Correlation analysis was conducted between network properties and BMI for the overweight/obese subjects. Compared with normal weight subjects, overweight/obese subjects exhibited altered network connectivity strength in four network nodes, namely the pancreas (p = 0.033), spleen (p = 0.021), visceral adipose tissue (VAT) (p = 1.12 × 10-5) and bone (p = 0.021). Network deviations of overweight/obese subjects from the normal weight were positively correlated with BMI (r = 0.718, p = 3.64 × 10-5). In addition, overweight/obese subjects experienced altered connections between organs, and some of the altered connections, including pancreas-right lung and VAT-bilateral lung connections were significantly correlated with BMI. Overweight/obese individuals exhibit metabolic alterations in organ level, and altered metabolic interactions at the systemic level. The proposed approach using total-body PET imaging can reveal individual metabolic variability and metabolic deviations between organs, which would open up a new path for understanding metabolic alterations in overweight and obesity.

A Protocol for Simultaneous In Vivo Imaging of Cardiac and Neuroinflammation in Dystrophin-Deficient MDX Mice Using [18F]FEPPA PET.

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by dystrophin loss-notably within muscles and the central neurons system. DMD presents as cognitive weakness, progressive skeletal and cardiac muscle degeneration until pre-mature death from cardiac or respiratory failure. Innovative therapies have improved life expectancy; however, this is accompanied by increased late-onset heart failure and emergent cognitive degeneration. Thus, better assessment of dystrophic heart and brain pathophysiology is needed. Chronic inflammation is strongly associated with skeletal and cardiac muscle degeneration; however, neuroinflammation's role is largely unknown in DMD despite being prevalent in other neurodegenerative diseases. Here, we present an inflammatory marker translocator protein (TSPO) positron emission tomography (PET) protocol for in vivo concomitant assessment of immune cell response in hearts and brains of a dystrophin-deficient mouse model [mdx:utrn(+/-)]. Preliminary analysis of whole-body PET imaging using the TSPO radiotracer, [18F]FEPPA in four mdx:utrn(+/-) and six wildtype mice are presented with ex vivo TSPO-immunofluorescence tissue staining. The mdx:utrn(+/-) mice showed significant elevations in heart and brain [18F]FEPPA activity, which correlated with increased ex vivo fluorescence intensity, highlighting the potential of TSPO-PET to simultaneously assess presence of cardiac and neuroinflammation in dystrophic heart and brain, as well as in several organs within a DMD model.

Multiparametric dynamic whole-body PSMA PET/CT using [68Ga]Ga-PSMA-11 and [18F]PSMA-1007

BackgroundRoutine prostate-specific membrane antigen (PSMA) positron emission tomography (PET) performed for primary staging or restaging of prostate cancer patients is usually done as a single static image acquisition 60 min after tracer administration. In this study, we employ dynamic whole-body (D-WB) PET imaging to compare the pharmacokinetics of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 in various tissues and lesions, and to assess whether Patlak parametric images are quantitative and improve lesion detection and image readability.MethodsTwenty male patients with prostate cancer were examined using a D-WB PSMA PET protocol. Ten patients were scanned with [68Ga]Ga-PSMA-11 and ten with [18F]PSMA-1007. Kinetic analyses were made using time-activity curves (TACs) extracted from organs (liver, spleen, bone, and muscle) and lesions. For each patient, three images were produced: SUV + Patlak parametric images (Ki and DV). All images were reviewed visually to compare lesion detection, image readability was quantified using target-to-background ratios (TBR), and Ki and DV values were compared.ResultsThe two PSMA tracers exhibited markedly different pharmacokinetics in organs: reversible for [68Ga]Ga-PSMA-11 and irreversible for [18F]PSMA-1007. For both tracers, lesions kinetics were best described by an irreversible model. All parametric images were of good visual quality using both radiotracers. In general, Ki images were characterized by reduced vascular signal and increased lesion TBR compared with SUV images. No additional malignant lesions were identified on the parametric images.ConclusionD-WB PET/CT is feasible for both PSMA tracers allowing for direct reconstruction of parametric Ki images. The use of multiparametric PSMA images increased TBR but did not lead to the detection of more lesions. For quantitative whole-body Ki imaging, [18F]PSMA-1007 should be preferred over [68Ga]Ga-PSMA-11 due to its irreversible kinetics in organs and lesions.

Respiratory-gated 18F Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging in Evaluation of Primary Gastric Lesions and Gastric Lymph Nodes in Patients with Gastric Cancer

AimsTo evaluate the added value of respiratory-gated positron emission tomography (PET) in 18F fluorodeoxyglucose (FDG) PET/magnetic resonance imaging (MRI) in the visual and semi-quantitative assessment of primary gastric lesions and gastric lymph nodes for patients with gastric cancer. Materials and methodsIn total, 102 upper abdominal respiratory-gated and whole-body 18F FDG PET/MRI of 88 patients with gastric cancer were evaluated visually and semi-quantitatively. For 41 patients who underwent surgery, histopathological and PET findings were compared. Three PET images were obtained from upper abdominal PET data: non-Q static (non-QS) PET from all counts, respiratory-gated Q static (QS) PET from counts in the end-expiration phase of breathing, shortened 4 min (S4min) PET that was reconstructed to obtain similar counts to QS PET. The semi-quantitative parameters (standardised uptake values, metabolic tumour volume, total lesion glycolysis) of primary lesions for each PET image, the sizes of primary lesions and the patient's body mass index were recorded. According to lymph node stations, the presence and numbers of positive lymph nodes and visual scores of lymph nodes for each PET image were recorded. ResultsThe patients with smaller gastric lesions (≤30 mm) or higher body mass index (>30) had significantly higher standardised uptake value percentage changes in QS PET compared with non-QS PET (all P < 0.05). The third (lesser curvature), fourth (greater curvature) and sixth (infra-pyloric) lymph node stations had significantly higher visual scores in the QS PET than in the others. The fourth lymph node station had a significantly higher number of FDG-positive lymph node in the QS PET than in the non-QS and the whole-body PET images. In the fourth station, sensitivity, positive predictive value, negative predictive value and accuracy increased in the QS PET compared with the others. ConclusionRespiratory-gated PET/MRI was found to be significantly superior in the evaluation of especially the fourth lymph node station, smaller gastric lesions and in the patients with a higher BMI compared with the non-respiratory-gated PET images.

Parametric Imaging of Biologic Activity of Atherosclerosis Using Dynamic Whole-Body Positron Emission Tomography

BackgroundFor molecular imaging of atherosclerotic vessel wall activity, tracer kinetic analysis may yield improved contrast versus blood, more robust quantitative parameters, and more reliable characterization of systems biology. ObjectivesThe authors introduce a novel dynamic whole-body positron emission tomography (PET) protocol that is enabled by rapid continuous camera table motion, followed by reconstruction of parametric data sets using voxel-based Patlak graphical analysis. MethodsTwenty-five subjects were prospectively enrolled and underwent dynamic PET up to 90 minutes after injection of 2-[18F]fluoro-2-deoxy-D-glucose (FDG). Two sets of images were generated: 1) the established standard of static standardized uptake value (SUV) images; and 2) parametric images of the metabolic rate of FDG (MRFDG) using the Patlak plot–derived influx rate. Arterial wall signal was measured and compared using the volume-of-interest technique, and its association with hematopoietic and lymphoid organ signal and atherosclerotic risk factors was explored. ResultsParametric MRFDG images provided excellent arterial wall visualization, with elimination of blood-pool activity, and enhanced focus detectability and reader confidence. Target-to-background ratio (TBR) from MRFDG images was significantly higher compared with SUV images (2.6 ± 0.8 vs 1.4 ± 0.2; P < 0.0001), confirming improved arterial wall contrast. On MRFDG images, arterial wall signal showed improved correlation with hematopoietic and lymphoid organ activity (spleen P = 0.0009; lymph nodes P = 0.0055; and bone marrow P = 0.0202) and increased with the number of atherosclerotic risk factors (r = 0.49; P = 0.0138), where signal from SUV images (SUVmaxP = 0.9754; TBRmaxP = 0.8760) did not. ConclusionsAbsolute quantification of MRFDG is feasible for arterial wall using dynamic whole-body PET imaging. Parametric images provide superior arterial wall contrast, and they might be better suited to explore the relationship between arterial wall activity, systemic organ networks, and cardiovascular risk. This novel methodology may serve as a platform for future diagnostic and therapeutic clinical studies targeting the biology of arterial wall disease.

Evaluation of a High-Sensitivity Organ-Targeted PET Camera

The aim of this study is to evaluate the performance of the Radialis organ-targeted positron emission tomography (PET) Camera with standardized tests and through assessment of clinical-imaging results. Sensitivity, count-rate performance, and spatial resolution were evaluated according to the National Electrical Manufacturers Association (NEMA) NU-4 standards, with necessary modifications to accommodate the planar detector design. The detectability of small objects was shown with micro hotspot phantom images. The clinical performance of the camera was also demonstrated through breast cancer images acquired with varying injected doses of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) and qualitatively compared with sample digital full-field mammography, magnetic resonance imaging (MRI), and whole-body (WB) PET images. Micro hotspot phantom sources were visualized down to 1.35 mm-diameter rods. Spatial resolution was calculated to be 2.3 ± 0.1 mm for the in-plane resolution and 6.8 ± 0.1 mm for the cross-plane resolution using maximum likelihood expectation maximization (MLEM) reconstruction. The system peak noise equivalent count rate was 17.8 kcps at a 18F-FDG concentration of 10.5 kBq/mL. System scatter fraction was 24%. The overall efficiency at the peak noise equivalent count rate was 5400 cps/MBq. The maximum axial sensitivity achieved was 3.5%, with an average system sensitivity of 2.4%. Selected results from clinical trials demonstrate capability of imaging lesions at the chest wall and identifying false-negative X-ray findings and false-positive MRI findings, even at up to a 10-fold dose reduction in comparison with standard 18F-FDG doses (i.e., at 37 MBq or 1 mCi). The evaluation of the organ-targeted Radialis PET Camera indicates that it is a promising technology for high-image-quality, low-dose PET imaging. High-efficiency radiotracer detection also opens an opportunity to reduce administered doses of radiopharmaceuticals and, therefore, patient exposure to radiation.

Cycle-consistent learning-based hybrid iterative reconstruction for whole-body PET imaging

Objective. To develop a cycle-consistent learning-based hybrid iterative reconstruction (IR) method that takes only slightly longer than analytic reconstruction, while pursuing the image resolution and tumor quantification achievable by IR for whole-body PET imaging. Approach. We backproject the raw positron emission tomography (PET) data to generate a blurred activity distribution. From the backprojection to the IR label, a reconstruction mapping that approximates the deblurring filters for the point spread function and the physical effects of the PET system is unrolled to a neural network with stacked convolutional layers. By minimizing the cycle-consistent loss, we train the reconstruction and inverse mappings simultaneously. Main results. In phantom study, the proposed method results in an absolute relative error (RE) of the mean activity of 4.0% ± 0.7% in the largest hot sphere, similar to the RE of the full-count IR and significantly smaller than that obtained by CycleGAN postprocessing. Achieving a noise reduction of 48.1% ± 0.5% relative to the low-count IR, the proposed method demonstrates advantages over the low-count IR and CycleGAN in terms of resolution maintenance, contrast recovery, and noise reduction. In patient study, the proposed method obtains a noise reduction of 44.6% ± 8.0% for the lung and the liver, while maintaining the regional mean activity in both simulated lesions and real tumors. The run time of the proposed method is only half that of the conventional IR. Significance. The proposed cycle-consistent learning from the backprojection rather than the raw PET data or an IR result enables improved reconstruction accuracy, reduced memory requirements, and fast implementation speeds for clinical whole-body PET imaging.

64Cu]Cu-Albumin Clearance Imaging to Evaluate Lymphatic Efflux of Cerebrospinal Space Fluid in Mouse Model.

Clearance of brain waste in the cerebrospinal fluid (CSF) through the meningeal lymphatic vessels (mLV) has been evaluated mostly through the fluorescent imaging which has inherent limitations in the context of animal physiology and clinical translatability. The study aimed to establish molecular imaging for the evaluation of mLV clearance function. Radionuclide imaging after intrathecal (IT) injection was acquired in C57BL/6 mice of 2-9 months. The distribution of [99mTc]Tc-diethylenetriamine pentaacetate (DTPA) and [64Cu]Cu-human serum albumin (HSA) was comparatively evaluated. Evans Blue and [64Cu]Cu-HSA were used to evaluate the distribution of tracer under various speed and volume conditions. [99mTc]Tc-DTPA is not a suitable tracer for evaluation of CSF clearance via mLV as no cervical lymph node uptake was observed while it was cleared from the body. A total volume of 3 to 9 μL at an infusion rate of 300 to 500 nL/min was not sufficient for the tracer to reach the cranial subarachnoid space and clear throughout the mLV. As a result, whole-body positron emission tomography imaging using [64Cu]Cu-HSA at 700 nL/min, to deliver 6 μL of injected volume, was set for characterization of the CSF to mLV clearance. Through this protocol, the mean terminal CSF clearance half-life was measured to be 123.6 min (range 117.0-135.0) in normal mice. We established molecular imaging to evaluate CSF drainage through mLV using [64Cu]Cu-HSA. This imaging method is expected to be extended in animal models of dysfunctional meningeal lymphatic clearance and translational research for disease-modifying therapeutic approaches. The online version contains supplementary material available at 10.1007/s13139-022-00746-6.

The Role of Positron Emission Tomography in Bariatric Surgery Research: a Review.

Bariatric surgery, initially understood as restricting or bypassing the amount of food that reaches the stomach to reduce food intake and/or increase malabsorption of food to promote weight loss, is now recognized to also affect incretin signaling in the gut and promote improvements in system-wide metabolism. Positron emission tomography (PET) is an imaging technique whereby patients are injected with picomolar concentrations of radioactive molecules, below the threshold of having physiological effects, to measure spatial distributions of blood flow, metabolism, receptor, and enzyme pharmacology. Recent advances in both whole-body PET imaging and radioligand development will allow for novel research that may help clarify the roles of peripheral and central receptor/enzyme systems in treating obesity with bariatric surgery.

Positron Emission Tomography-Magnetic Resonance Imaging Pharmacokinetics, In Vivo Biodistribution, and Whole-Body Elimination of Mn-PyC3A.

Mn-PyC3A is an experimental manganese (Mn)-based extracellular fluid magnetic resonance imaging (MRI) contrast agent that is being evaluated as a direct replacement for clinical gadolinium (Gd)-based contrast agents. The goals of this study were to use simultaneous positron emission tomography (PET)-MRI to (1) compare the whole-body pharmacokinetics, biodistribution, and elimination of Mn-PyC3A with the liver-specific contrast agent mangafodipir (Mn-DPDP), (2) determine the pharmacokinetics and fractional excretion of Mn-PyC3A in a rat model of renal impairment, and (3) compare whole-body elimination of Mn-PyC3A to gadoterate (Gd-DOTA) in a rat model of renal impairment. Mn-PyC3A and Mn-DPDP were radiolabeled with the positron emitting isotope Mn-52 via Mn2+ exchange with 52MnCl2. Dynamic simultaneous PET-MRI was used to measure whole-body pharmacokinetics and biodistribution of Mn-52 immediately and out to 7 days after an intravenous 0.2 mmol/kg dose of [52Mn]Mn-PyC3A to normal or to 5/6 nephrectomy rats or a 0.01 mmol/kg dose of [52Mn]Mn-DPDP to normal rats. The fractional excretion and 1- and 7-day biodistribution in rats after the injection of 2.0 mmol/kg [52Mn]Mn-PyC3A (n = 11 per time point) or 2.0 mmol/kg Gd-DOTA (n = 8 per time point) were quantified by gamma counting or Gd elemental analysis, respectively. Comparisons of Mn-PyC3A pharmacokinetics and in vivo biodistribution in normal and 5/6 nephrectomy rats and comparisons of ex vivo Mn versus Gd biodistribution data in 5/6 nephrectomy were made with an unpaired t test. Dynamic PET-MRI data demonstrate that both [52Mn]Mn-PyC3A and [52Mn]Mn-DPDP were eliminated by mixed renal and hepatobiliary elimination but that a greater fraction of [52Mn]Mn-PyC3A was eliminated by renal filtration. Whole-body PET images show that Mn-52 from [52Mn]Mn-PyC3A was efficiently eliminated from the body, whereas Mn-52 from [52Mn]Mn-DPDP was retained throughout the body. The blood elimination half-life of [52Mn]Mn-PyC3A in normal and 5/6 nephrectomy rats was 13 ± 3.5 minutes and 23 ± 12 minutes, respectively (P = 0.083). Area under the curve between 0 and 60 minutes postinjection (AUC0-60) in the bladder of normal and 5/6 nephrectomy rats was 2600 ± 1700 %ID/cc*min and 750 ± 180 %ID/cc*min, respectively (P = 0.024), whereas AUC0-60 in the liver of normal and 5/6 nephrectomy rats was 33 ± 13 %ID/cc*min and 71 ± 16 %ID/cc*min, respectively (P = 0.011), indicating increased hepatobiliary elimination in 5/6 nephrectomy rats. The %IDs of Mn from [52Mn]Mn-PyC3A and Gd from Gd-DOTA recovered from 5/6 nephrectomy rats 1 day after injection were 2.0 ± 1.1 and 1.3 ± 0.34, respectively (P = 0.10) and 7 days after injection were 0.14 ± 0.11 and 0.41 ± 0.24, respectively (P = 0.0041). Mn-PyC3A has different pharmacokinetics and is more efficiently eliminated than Mn-DPDP in normal rats. Mn-PyC3A is efficiently eliminated from both normal and 5/6 nephrectomy rats, with increased fractional hepatobiliary excretion from 5/6 nephrectomy rats. Mn-PyC3A is more completely eliminated than Gd-DOTA from 5/6 nephrectomy rats after 7 days.

Deep learning-based attenuation correction in the absence of structural information for whole-body positron emission tomography imaging

Deriving accurate structural maps for attenuation correction (AC) of whole-body positron emission tomography (PET) remains challenging. Common problems include truncation, inter-scan motion, and erroneous transformation of structural voxel-intensities to PET µ-map values (e.g. modality artifacts, implanted devices, or contrast agents). This work presents a deep learning-based attenuation correction (DL-AC) method to generate attenuation corrected PET (AC PET) from non-attenuation corrected PET (NAC PET) images for whole-body PET imaging, without the use of structural information. 3D patch-based cycle-consistent generative adversarial networks (CycleGAN) is introduced to include NAC-PET-to-AC-PET mapping and inverse mapping from AC PET to NAC PET, which constrains NAC-PET-to-AC-PET mapping to be closer to one-to-one mapping. Since NAC PET images share similar anatomical structures to the AC PET image but lack contrast information, residual blocks, which aim to learn the differences between NAC PET and AC PET, are used to construct generators of CycleGAN. After training, patches from NAC PET images were fed into NAC-PET-to-AC-PET mapping to generate DL-AC PET patches. DL-AC PET image was then reconstructed through patch fusion. We conducted a retrospective study on 55 datasets of whole-body PET/CT scans to evaluate the proposed method. In comparing DL-AC PET with original AC PET, average mean error (ME) and normalized mean square error (NMSE) of the whole-body were 0.62% ± 1.26% and 0.72% ± 0.34%. The average intensity changes measured on sequential PET images with AC and DL-AC on both normal tissues and lesions differ less than 3%. There was no significant difference of the intensity changes between AC and DL-AC PET, which demonstrate DL-AC PET images generated by the proposed DL-AC method can reach a same level to that of original AC PET images. The method demonstrates excellent quantification accuracy and reliability and is applicable to PET data collected on a single PET scanner or hybrid platform with computed tomography (PET/CT) or magnetic resonance imaging (PET/MRI).

Spatially guided nonlocal mean approach for denoising of PET images.

Nonlocal mean (NLM) filtering proved to be an effective tool for noise reduction in natural and medical imaging. The technique relies on existing redundant information in the input image to discriminate the genuine signal from noise. However, due to the prohibitively long computation time, the search for finding similar information is confined by a predefined search window, which may hamper the performance of this filter. In this work, a spatially guided non local mean (SG-NLM) approach was proposed to overcome this issue. The proposed method was evaluated on whole-body positron emission tomography images presenting with high noise levels, which adversely affect lesion detectability and quantitative accuracy. In the SG-NLM method, as opposed to the conventional NLM method, where a predefined search window is defined to confine exhaustive search for finding similar patterns, the information about similar patterns is extracted from the clustered version (created based on signal intensity levels) of the input image as well as information about prominent edges. The performance of the SG-NLM was evaluated against post-reconstruction NLM, Gaussian, bilateral and BayesShrink Wavelet denoising approaches. A digital phantom containing three small inserts mimicking lesions in the lung, experimental study using the Jaszczak phantom and whole-body PET/CT clinical studies were utilized to assess the performance of abovementioned denoising approaches. The SG-NLM method led to a signal-to-noise (SNR) increase from 21.3 (unfiltered PET image) to 30.1 in computer simulations of small lesions while the NLM mean filer resulted in an SNR of 29.4 (P<0.05). The experimental Jaszczak phantom study demonstrated that the contrast-to-noise ratio (CNR) increased from 11.3 when using the Gaussian filter to 18.6 and 19.5 when using NLM and SG-NLM filters (P<0.05), respectively. The superior performance of the SG-NLM approach was confirmed by clinical studies where the bias in malignant lesions decreased to -2.3±1.1% compared to -11.7±2.4 and -2.9±1.1 achieved using the Gaussian and NLM methods (P<0.05), respectively. The proposed SG-NLM achieves promising compromise between noise reduction and signal preservation compared to the conventional NLM method. The superior performance of the SG-NLM method was accomplished without adding extra burden to the computational complexity of the conventional NLM filter, which makes it attractive for denoising PET images.

Error evaluation of the D-shuttle dosimeter technique in positron emission tomography study

The D-shuttle dosimeter technique is a convenient approach for estimating the radiation dosimetry in a positron emission tomography (PET) study that employs multiple D-shuttle dosimeters attached to the body surface of a patient. To bring this technique into clinical usage, it is very important to evaluate its performance by investigating the bias associated with D-shuttle dosimeter positioning and by comparing the estimates with those of the whole-body dynamic PET imaging technique. The torso cavity and six spheres of the NEMA body phantom were filled with 18F-FDG solution, and then, the phantom was imaged for 1h. We assumed the mislocated positioning of the D-shuttle dosimeters by shifting them in the z-direction (upper) in a range of 1-5cm from the original positions. The cumulative radioactivities, absorbed doses, and effective dose were estimated using accurate and mislocated positions of the D-shuttle dosimeters. For comparison, the cumulative radioactivities were also estimated from the PET images, and then, the absorbed doses and effective dose were computed. The maximum bias of the average estimated cumulated radioactivities and the effective doses was - 15.0% and - 19.7% for the 1cm shifted positions, respectively. The ratios of absorbed doses obtained from D-shuttle and PET measurement against the actual values were between 0.9 and 1.3, and 0.7 and 1.0, respectively. The bias associated with the D-shuttle dosimeter positions was significant and probably consistent, and both dosimetric techniques exhibited good performance in this phantom study.

A Pyropheophorbide Analogue Containing a Fused Methoxy Cyclohexenone Ring System Shows Promising Cancer-Imaging Ability.

Herein we report the synthesis, photophysical properties, positron emission tomography (PET) imaging and photodynamic therapy (PDT) efficacy of methyl 3-(1'-m-iodobenzyloxy)ethyl-3-devinyl-verdin 4 (with or without the 124 I isotope). The PET imaging ability and ex vivo biodistribution of [124 I]4 were compared with the well-studied methyl [3-(124 1'-m-iodobenzyloxy)ethyl]-3-devinyl-pyropheophorbide-a methyl ester (PET-ONCO or [124 I]2) and [18 F]fluorodeoxyglucose ([18 F]FDG) in BALB/c mice bearing colon-26 tumors. Whole-body PET images of [124 I]4 containing a fused methoxy cyclohexenone ring system showed excellent tumor contrast with time (72>48>24 h post-injection). Ex vivo biodistribution results indicate that relative to the current clinical standard [18 F]FDG and [124 I]2 in 2 % ethanol formulation, [124 I]4, at the same radioactive dose (25 μCi per mouse), showed higher tumor uptake at 24 h post-injection and longer tumor retention. In biological environments, compound 4 showed lower fluorescence and lower singlet oxygen yield than 2, which is possibly due to higher aggregation caused by the presence of a fused cyclohexenone ring system, resulting in limited in vitro/in vivo PDT efficacy. Therefore, the chlorophyll-a analogue [124 I]4 provides easy access to a novel PET imaging agent (with no skin phototoxicity) to image cancer types-brain, renal carcinomas, pancreas-in which [18 F]FDG shows limitations.

Tumor Microenvironment-Activated Ultrasensitive Nanoprobes for Specific Detection of Intratumoral Glutathione by Ratiometric Photoacoustic Imaging

Glutathione (GSH), one of the most significant reducing species in vivo, plays important roles in a variety of diseases and cellular functions. Precise quantification of GSH via advanced noninvasive photoacoustic imaging (PAI) is of vital significance for the early diagnosis and prompt treatment of GSH-related deep-seated diseases, which stresses the need for custom-design of GSH-sensitive PAI probes with changeable near-infrared spectroscopy (NIR) absorption. In this work, a novel intelligent tumor microenvironment-activated ratiometric PAI nanoprobe is first developed with the intention of specific ultrasensitive detection of intratumoral GSH by overcoming the limitations of previously reported fluorescent or PA imaging sensors. This special ratiometric PAI nanoprobe (CR-POM) is synthesized through the self-assembly of croconaine (CR) dye and molybdenum-based polyoxometalate (POM) clusters with opposite NIR absorbance change in response to GSH. The resulting amplified ratiometric absorbance (Ab866/Ab700), the relatively low limit of detection value (0.51 mM), and the unique acidity-activated self-aggregation contribute to the prolonged intratumoral retention and enhanced tumor accumulation of CR-POM for accurate quantification of intratumoral GSH (0.5-10 mM). Featuring the additional merit of 64Cu radiolabeling for whole-body positron-emission tomography imaging, the smartly designed CR-POM nanoprobe will open new horizons for real-time noninvasive monitoring of biodistribution and simultaneous accurate quantification of GSH levels, especially in tumor and other GSH-related pathophysiological processes.

Dynamic whole-body PET imaging: principles, potentials and applications.

In this article, we discuss dynamic whole-body (DWB) positron emission tomography (PET) as an imaging tool with significant clinical potential, in relation to conventional standard uptake value (SUV) imaging. DWB PET involves dynamic data acquisition over an extended axial range, capturing tracer kinetic information that is not available with conventional static acquisition protocols. The method can be performed within reasonable clinical imaging times, and enables generation of multiple types of PET images with complementary information in a single imaging session. Importantly, DWB PET can be used to produce multi-parametric images of (i) Patlak slope (influx rate) and (ii) intercept (referred to sometimes as "distribution volume"), while also providing (iii) a conventional 'SUV-equivalent' image for certain protocols. We provide an overview of ongoing efforts (primarily focused on FDG PET) and discuss potential clinically relevant applications. Overall, the framework of DWB imaging [applicable to both PET/CT(computed tomography) and PET/MRI (magnetic resonance imaging)] generates quantitative measures that may add significant value to conventional SUV image-derived measures, with limited pitfalls as we also discuss in this work.