Frontiers in nuclear medicine (Lausanne, Switzerland)最新文献

Lung scan is an accurate and noninvasive tool for evaluating the distribution of lung perfusion. We present a rare case of total absence of perfusion on lung scan to the right lung with two contralateral defects due to severe occlusion of the right pulmonary artery, as well as segmental arteries in the left lung in a young female woman diagnosed with Takayasu Arteritis. We highlight the similarities of the findings between pulmonary arteritis in Takayasu disease and thromboembolic disease and the importance of careful interpretation of perfusion lung scan in order to avoid misdiagnosis that could endanger the patient's life.

Prostate gland segmentation is the primary step to estimate gland volume, which aids in the prostate disease management. In this study, we present a 2D-3D convolutional neural network (CNN) ensemble that automatically segments the whole prostate gland along with the peripheral zone (PZ) (PPZ-SegNet) using a T2-weighted sequence (T2W) of Magnetic Resonance Imaging (MRI). The study used 4 different public data sets organized as Train #1 and Test #1 (independently derived from the same cohort), Test #2, Test #3 and Test #4. The prostate gland and the peripheral zone (PZ) anatomy were manually delineated with consensus read by a radiologist, except for Test #4 cohorts that had pre-marked glandular anatomy. A Bayesian hyperparameter optimization method was applied to construct the network model (PPZ-SegNet) with a training cohort (Train #1, n = 150) using a five-fold cross validation. The model evaluation was performed on an independent cohort of 283 T2W MRI prostate cases (Test #1 to #4) without any additional tuning. The data cohorts were derived from The Cancer Imaging Archives (TCIA): PROSTATEx Challenge, Prostatectomy, Repeatability studies and PROMISE12-Challenge. The segmentation performance was evaluated by computing the Dice similarity coefficient and Hausdorff distance between the estimated-deep-network identified regions and the radiologist-drawn annotations. The deep network architecture was able to segment the prostate gland anatomy with an average Dice score of 0.86 in Test #1 (n = 192), 0.79 in Test #2 (n = 26), 0.81 in Test #3 (n = 15), and 0.62 in Test #4 (n = 50). We also found the Dice coefficient improved with larger prostate volumes in 3 of the 4 test cohorts. The variation of the Dice scores from different cohorts of test images suggests the necessity of more diverse models that are inclusive of dependencies such as the gland sizes and others, which will enable us to develop a universal network for prostate and PZ segmentation. Our training and evaluation code can be accessed through the link: https://github.com/mariabaldeon/PPZ-SegNet.git.

Introduction: Molecular imaging has not been used to support the development of drugs for the treatment of pulmonary disorders. The aim of the present translational study was to advance quantitative pulmonary PET imaging by demonstrating occupancy of the reference asthma drug tiotropium at muscarinic acetylcholine receptors (mAChR).

Methods: PET imaging was performed using the muscarinic radioligand [¹¹C]VC-002. The key methodological step involved estimating muscarinic receptor binding while disentangling it from the background of non-specific binding. The relationship between tiotropium exposure and receptor occupancy (RO) was assessed in non-human primates (NHPs) after intravenous injection of tiotropium doses at a broad dose interval (0.03-1 µg/kg). The feasibility of measuring RO in the human lung was then confirmed in seven healthy human subjects after inhalation of a single therapeutic dose of tiotropium (18 µg).

Results: There was an evident effect of tiotropium on [¹¹C]VC-002 binding to mAChRs in lungs in both NHPs and humans. In NHPs, RO was 11 to 78% and increased in a dose dependent manner. Non-displaceable binding in NHPs was about 10% of total binding. In humans, RO was 6%-65%, and non-displaceable binding was about 20% of total binding at baseline.

Discussion: The results demonstrate that [¹¹C]VC-002 binds specifically to mAChRs in the lungs enabling the assessment of RO following administration of muscarinic antagonist drugs. Furthermore, the methodology has potential not only for dose finding and comparison of drug formulations in future applied studies, but also for evaluating changes in lung receptor distribution during disease or in response to therapy.

Clinical trial registration: ClinicalTrials.gov, identifier: NCT03097380.

A 61-year-old woman with a history of metastatic follicular thyroid carcinoma became radioiodine-refractory following two doses of radioiodine (RAI) therapy (cumulative = 230 mCi). While no RAI-avid lesion was noticed in the last post-ablation whole-body radioiodine scan (WBIS), she reported sternal pain, which was accompanied by rapidly rising thyroglobulin levels. ¹⁸F-FDG and ⁶⁸Ga-DOTA-TATE PET/CT was performed, showing metastatic pulmonary nodules and a lytic sternal lesion with acceptable avidity (i.e. uptake ≥ liver). Following four cycles of peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTA-TATE, the thyroglobulin levels dropped significantly, and the sternal pain was partially alleviated. Despite only experiencing grade I thrombocytopenia, the treating physician decided to discontinue PRRT and repeat the diagnostic WBIS. Surprisingly, the scan revealed significantly increased tracer uptake in the sternum. The patient received 200 mCi ¹³¹I, and WBIS showed increased RAI uptake in all pulmonary nodules as well as bone metastases. We report a case of RAI-refractory thyroid carcinoma with a somatostatin-receptor expression that re-differentiated and gained significant RAI uptake capacity after PRRT.

Purpose: We present a probabilistic approach to medical image analysis that requires, and makes use of, explicit prior information provided by a medical expert. Depending on the choice of prior model the method can be used for image enhancement, analysis, and segmentation.

Methods: The methodology is based on a probabilistic approach to medical image analysis, that allows integration of 1) arbitrarily complex prior information (for which realizations can be generated), 2) information about a convolution operator of the imaging system, and 3) information about the noise in the reconstructed image into a posterior probability density. The method was demonstrated on positron emission tomography (PET) images obtained from a phantom and a patient with lung cancer. The likelihood model (multivariate log-normal) and the convolution operator were derived from phantom data. Two examples of prior information were used to show the potential of the method. The extended Metropolis-Hastings algorithm, a Markov chain Monte Carlo method, was used to generate realizations of the posterior distribution of the tracer activity concentration.

Results: A set of realizations from the posterior was used as the base of a quantitative PET image analysis. The mean and variance of activity concentrations were computed, as well as the probability of high tracer uptake and statistics on the size and activity concentration of high uptake regions. For both phantom and in vivo images, the estimated images of mean activity concentrations appeared to have reduced noise levels, and a sharper outline of high activity regions, as compared to the original PET. The estimated variance of activity concentrations was high at the edges of high activity regions.

Conclusions: The methodology provides a probabilistic approach for medical image analysis that explicitly takes into account medical expert knowledge as prior information. The presented first results indicate the potential of the method to improve the detection of small lesions. The methodology allows for a probabilistic measure of the size and activity level of high uptake regions, with possible long-term perspectives for early detection of cancer, as well as treatment, planning, and follow-up.

Infection of native tissues or implanted devices is common, but clinical diagnosis is frequently difficult and currently available noninvasive tests perform poorly. Immunocompromised individuals (for example transplant recipients, or those with cancer) are at increased risk. No imaging test in clinical use can specifically identify infection, or accurately differentiate bacterial from fungal infections. Commonly used [¹⁸F]fluorodeoxyglucose (18FDG) positron emission computed tomography (PET/CT) is sensitive for infection, but limited by poor specificity because increased glucose uptake may also indicate inflammation or malignancy. Furthermore, this tracer provides no indication of the type of infective agent (bacterial, fungal, or parasitic). Imaging tools that directly and specifically target microbial pathogens are highly desirable to improve noninvasive infection diagnosis and localization. A growing field of research is exploring the utility of radiometals and their chelators (siderophores), which are small molecules that bind radiometals and form a stable complex allowing sequestration by microbes. This radiometal-chelator complex can be directed to a specific microbial target in vivo, facilitating anatomical localization by PET or single photon emission computed tomography. Additionally, bifunctional chelators can further conjugate therapeutic molecules (e.g., peptides, antibiotics, antibodies) while still bound to desired radiometals, combining specific imaging with highly targeted antimicrobial therapy. These novel therapeutics may prove a useful complement to the armamentarium in the global fight against antimicrobial resistance. This review will highlight current state of infection imaging diagnostics and their limitations, strategies to develop infection-specific diagnostics, recent advances in radiometal-based chelators for microbial infection imaging, challenges, and future directions to improve targeted diagnostics and/or therapeutics.

IgG4-related disease is a fibrous-inflammatory process belonging to immunomodulation disorders. We report a case of a 57-year-old man with the IgG4-related disease (RD). ⁶⁸Ga-FAPI-04 PET/CT showed more significant uptake in most lesions than in ¹⁸F-FDG PET/CT except for the cervical and mediastinal lymph nodes. Besides, uptake in the submandibular glands were only detected in ⁶⁸Ga-FAPI-04 PET/CT. The biopsy result of the cervical lymph nodes confirmed the diagnosis of IgG4-related disease. After treatment, only slight FDG-avid cervical lymph nodes were observed in the ¹⁸F-FDG PET/CT, while the raised uptake of ⁶⁸Ga-FAPI-04 could be observed in the pancreas and submandibular glands. ⁶⁸Ga-FAPI-04 PET-CT might have promising applications in evaluating IgG4-RD, whether in initial or follow-up imaging during steroid therapy.

Introduction: Alzheimer's disease (AD) is characterized by the misfolding and aggregation of two major proteins: amyloid-beta (Aβ) and tau. Antibody-based PET radioligands are desirable due to their high specificity and affinity; however, antibody uptake in the brain is limited by the blood-brain barrier (BBB). Previously, we demonstrated that antibody transport across the BBB can be facilitated through interaction with the transferrin receptor (TfR), and the bispecific antibody-based PET ligands were capable of detecting Aβ aggregates via ex vivo imaging. Since tau accumulation in the brain is more closely correlated with neuronal death and cognition, we report here our strategies to prepare four F-18-labeled specifically engineered bispecific antibody probes for the selective detection of tau and Aβ aggregates to evaluate their feasibility and specificity, particularly for in vivo PET imaging.

Methods: We first created and evaluated (via both in vitro and ex vivo studies) four specifically engineered bispecific antibodies, by fusion of single-chain variable fragments (scFv) of a TfR antibody with either a full-size IgG antibody of Aβ or tau or with their respective scFv. Using [¹⁸F]SFB as the prosthetic group, all four ¹⁸F-labeled bispecific antibody probes were then prepared by conjugation of antibody and [¹⁸F]SFB in acetonitrile/0.1 M borate buffer solution (final pH ~ 8.5) with an incubation of 20 min at room temperature, followed by purification on a PD MiniTrap G-25 size exclusion gravity column.

Results: Based on both in vitro and ex vivo evaluation, the bispecific antibodies displayed much higher brain concentrations than the unmodified antibody, supporting our subsequent F18-radiolabeling. [¹⁸F]SFB was produced in high yields in 60 min (decay-corrected radiochemical yield (RCY) 46.7 ± 5.4) with radiochemical purities of >95%, confirmed by analytical high performance liquid chromatography (HPLC) and radio-TLC. Conjugation of [¹⁸F]SFB and bispecific antibodies showed a 65%-83% conversion efficiency with radiochemical purities of 95%-99% by radio-TLC.

Conclusions: We successfully labeled four novel and specifically engineered bispecific antibodies with [¹⁸F]SFB under mild conditions with a high RCY and purities. This study provides strategies to create brain-penetrable F-18 radiolabeled antibody probes for the selective detection of tau and Aβ aggregates in the brain of transgenic AD mice via in vivo PET imaging.

Introduction: CZT cameras have enabled the noninvasive quantification of myocardial flow reserve (MFR), an important physiologic measure. This study aimed to compare myocardial perfusion SPECT (MPS) with or without MFR evaluation for the detection of obstructive coronary artery disease (CAD).

Methods: 48 patients with CAD (>50% obstruction) detected at invasive coronary angiography or CT angiography underwent dipyridamole MPS and MFR evaluation within 30 days. A 1-day protocol (rest-stress) was used to quantify MFR. The acquisition of dynamic rest and stress images was initiated simultaneously to 99mTc sestamibi injection (370 and 1,110 MBq, respectively), both lasting for 11 min, followed by 5-min imaging. Pharmacologic stress with dipyridamole (0.56 mg/kg for 4 min) was performed with the patient positioned in the CZT camera. The images were processed and time-activity curves were generated, calculating global and regional MFR in a semiautomatic software. A global or regional MFR <2 was considered abnormal. MPS perfusion images were classified as normal or abnormal. The images were interpreted by experienced physicians blinded to the results of MFR and coronary angiography/CT.

Results: Mean age of the population was 61 ± 9 years, 54.2% female. Twenty patients (41.7%) had single-vessel CAD, 22 (45.8%) 2-vessel CAD and 6 (12.5%), triple-vessel CAD. Among the 82 vessels with obstruction, 48 had perfusion abnormalities in MPS and 60 had reduced MFR, while among the normal vessels, had 54 normal MPS and 52 had preserved MFR. The sensitivity of MFR (69%) was higher than that of MPS (55.2%), without significant changes in specificity (86 vs. 83.7%).

Conclusions: MFR in the CZT camera is more sensitive for the detection of CAD than perfusion abnormalities in MPS, especially in patients with multivessel CAD.

The diagnosis of cardiac sarcoidosis (CS) remains challenging. While only a small fraction of patients with systemic sarcoidosis present with clinically symptomatic CS, cardiac involvement has been associated with adverse outcomes, such as ventricular arrhythmia, heart block, heart failure and sudden cardiac death. Despite the clinical relevance of having an early and accurate diagnosis of CS, there is no gold-standard technique available for the assessment of CS. Non-invasive PET and MR imaging have shown promise in the detection of different histopathological features of CS. More recently, the introduction of hybrid PET-MR scanners has enabled the acquisition of these hallmarks in a single scan, demonstrating higher sensitivity and specificity for CS detection and risk stratification than with either imaging modality alone. This article describes recent developments in hybrid PET-MR imaging for improving the diagnosis of CS and discusses areas of future development that could make cardiac PET-MRI the preferred diagnostic tool for the comprehensive assessment of CS.