Kidney dynamic SPECT acquisition on a CZT swiveling-detector ring camera: an in vivo pilot study.

BACKGROUND: Large field of view CZT SPECT cameras with a ring geometry are available for some years now. Thanks to their good sensitivity and high temporal resolution, general dynamic SPECT imaging may be performed more easily, without resorting to dedicated systems. To evaluate the dynamic SPECT imaging by such cameras, we have performed an in vivo pilot study to analyze the kidney function of a pig and compare the results to standard dynamic planar imaging by a conventional gamma camera. METHODS: A 7-week-old (12 kg) female Landrace pig was injected with [99mTc]Tc-MAG3 and a 30 min dynamic SPECT acquisition of the kidneys was performed on a CZT ring camera. A fast SPECT/CT was acquired with the same camera immediately after the dynamic SPECT, without moving the pig, and used for attenuation correction and drawing regions of interest. The next day the same pig underwent a dynamic planar imaging of the kidneys by a conventional 2-head gamma camera. The dynamic SPECT acquisition was reconstructed using a MLEM algorithm with up to 20 iterations, with and without attenuation correction. Time-activity curves of the total counts of each kidney were extracted from 2D and 3D dynamic images. An adapted 2-compartment model was derived to fit the data points and extract physiological parameters. Comparison of these parameters was performed between the different reconstructions and acquisitions. RESULTS: Time-activity curves were nicely fitted with the 2-compartment model taking into account the anesthesia and bladder filling. Kidney physiological parameters were found in agreement with literature values. Good agreement of these parameters was obtained for the right kidney between dynamic SPECT and planar imaging. Regional analysis of the kidneys can be performed in the case of the dynamic SPECT imaging and provided good agreement with the whole kidney results. CONCLUSIONS: Dynamic SPECT imaging is feasible with CZT swiveling-detector ring cameras and provides results in agreement with dynamic planar imaging by conventional gamma cameras. Regional analysis of organs uptake and clearance becomes possible. Further studies are required regarding the optimization of acquisition and reconstruction parameters to improve image quality and enable absolute quantification.

A large-volume low-pressure nasal irrigation delivers drug into the nasal cavity? An in vivo study.

The nasal administration route emerged as an interesting route in systemic and brain drug delivery, and different modalities of nasal delivery are available. The nasal irrigation is one of them, but there is a lack of studies investigating the distribution of a large-volume irrigation. The main aim of this study was to assess the deposition of radiolabeled saline in the nasal cavities and paranasal sinuses following nasal irrigation by imaging. Five healthy males volunteered to perform large-volume low-pressure nasal irrigation, with a douching device containing 50 mL of radiolabeled isotonic saline. Participants underwent a scintigraphy immediately after. Both the nasal cavities and maxillary sinuses were systematically reached by the solution during nasal irrigation. The sinuses set in a lower position during nasal irrigation showed a tendency to be more irrigated than the sinuses set in a higher position (7.67% vs 22.72%; p = 0.086). Moreover, substantial inter- and intraindividual heterogeneity regarding solution deposition was observed. Large-volume low-pressure nasal irrigation is a good modality to reach the maxillary sinuses as well as the nasal cavities. In order to ensure adequate reaching of both nasal cavities and paranasal sinuses, nasal irrigation should be performed bilaterally.

Inhaled drug delivery: a randomized study in intubated patients with healthy lungs.

BACKGROUND: The administration technique for inhaled drug delivery during invasive ventilation remains debated. This study aimed to compare in vivo and in vitro the deposition of a radiolabeled aerosol generated through four configurations during invasive ventilation, including setups optimizing drug delivery. METHODS: Thirty-one intubated postoperative neurosurgery patients with healthy lungs were randomly assigned to four configurations of aerosol delivery using a vibrating-mesh nebulizer and specific ventilator settings: (1) a specific circuit for aerosol therapy (SCAT) with the nebulizer placed at 30 cm of the wye, (2) a heated-humidified circuit switched off 30 min before the nebulization or (3) left on with the nebulizer at the inlet of the heated-humidifier, (4) a conventional circuit with the nebulizer placed between the heat and moisture exchanger filter and the endotracheal tube. Aerosol deposition was analyzed using planar scintigraphy. RESULTS: A two to three times greater lung delivery was measured in the SCAT group, reaching 19.7% (14.0-24.5) of the nominal dose in comparison to the three other groups (p < 0.01). Around 50 to 60% of lung doses reached the outer region of both lungs in all groups. Drug doses in inner and outer lung regions were significantly increased in the SCAT group (p < 0.01), except for the outer right lung region in the fourth group due to preferential drug trickling from the endotracheal tube and the trachea to the right bronchi. Similar lung delivery was observed whether the heated humidifier was switched off or left on. Inhaled doses measured in vitro correlated with lung doses (R = 0.768, p < 0.001). CONCLUSION: Optimizing the administration technique enables a significant increase in inhaled drug delivery to the lungs, including peripheral airways. Before adapting mechanical ventilation, studies are required to continue this optimization and to assess its impact on drug delivery and patient outcome in comparison to more usual settings.

[18F]FDG-PET/CT in Polymyalgia Rheumatica: An Update and Future Aspects.

Polymyalgia rheumatica (PMR) is an inflammatory disorder usually diagnosed in patients older than 50 years of age. It is characterized by sudden onset pain and prolonged morning stiffness in the scapular and/or pelvic girdle, sometimes debilitating and accompanied by constitutional symptoms such as weight loss. In approximately 20% of the cases, it is linked to giant cell arteritis (GCAV) representing a disease continuum. The diagnosis is mainly clinical and noninvasive imaging such as ultrasound of joints may be helpful. In atypical PMR cases, whole body imaging using [18F]FDG-PET/CT may be useful. First, to confirm or rule out the diagnosis of PMR, secondly, to assess the coexistence of a GCA, and thirdly to establish the differential diagnosis with other types of arthritides encountered in this age group, such as elderly-onset rheumatoid arthritis, spondyloarthropathies, crystal-induced arthropathies or the rare remittent seronegative symmetrical synovitis with pitting edema. Relatively typical patterns of [18F]FDG-PET/CT are well known, based on the clinical distribution of the disease (eg, scapular and pelvic girdle, interspinous bursae, sterno-costoclavicular joints, entheses), especially the hypermetabolism at the interspinous lumbar bursae that has shown the best post-test likelihood ratio in a meta-analysis. This article focuses on the differential diagnosis and on the visual and semi-quantitative tools that can be used to guide to the correct diagnosis of PMR as an add-on to the clinical picture. Further, we briefly discuss the options that can improve molecular imaging in the future for inflammatory rheumatisms in elderly.

Diagnostic Superiority of Dual-Time Point [18F]FDG PET/CT to Differentiate Malignant from Benign Soft Tissue Tumors.

[18F]FDG PET/CT is used in the workup of indeterminate soft tissue tumors (STTs) but lacks accuracy in the detection of malignant STTs. The aim of this study is to evaluate whether dual-time point [18F]FDG PET/CT imaging (DTPI) can be useful in this indication. In this prospective study, [18F]FDG PET/CT imaging was performed 1 h (t1) and 3 h (t2) after injection. Tumor uptake (SUVmax) was calculated at each time point to define a retention index (RI) corresponding to the variation between t1 and t2 (%). Sixty-eight patients were included, representing 20 benign and 48 malignant tumors (including 40 sarcomas). The RI was significantly higher in malignant STTs than in benign STTs (median: +21.8% vs. -2%, p < 0.001). An RI of >14.3% predicted STT malignancy with a specificity (Sp) of 90% and a sensitivity (Se) of 69%. An SUVmaxt1 of >4.5 was less accurate with an Sp of 80% and an Se of 60%. In a subgroup of tumors with at least mild [18F]FDG uptake (SUVmax ≥ 3; n = 46), the RI significantly outperformed the diagnostic accuracy of SUVmax (AUC: 0.88 vs. 0.68, p = 0.01). DTPI identifies malignant STT tumors with high specificity and outperforms the diagnostic accuracy of standard PET/CT.

Main challenges in radiation protection with emerging radionuclide therapies.

The recent development of radionuclide therapy and radioligand therapy has raised a call for achieving the highest quality standards, for either radiopharmacy or radiation protection. Novel radionuclides are now being used, either under the form of in-house production radiopharmaceuticals or available from companies. Over the last 20 years, they include radiolabeled microspheres for selective internal radiotherapy (SIRT), the introduction of the first commercially available alpha emitter radiopharmaceutical, 223Ra, and the radiosynoviorthesis which is highly variable across Europe. More important is the development of radioligand therapy, often called theranostics. In this concept, a diagnostic radiopharmaceutical can determine the chance of success of a therapeutic one. Typically, diagnostic radiopharmaceuticals for positron emission tomography, are labeled with 18F or 68Ga, such as the PSMA ligands or somatostatin analogs, and the therapeutic radiopharmaceutical is labeled with 177Lu. This has revolutionized the world of Nuclear Medicine, but also all concepts that shall be applied to properly apply quality assurance and radiation protection in the field. This article will follow the example of 131I as the main used radionuclide for therapy during the last 80 years. Proposals can be general, and in parallel expert's articles will give specific guidance on issues with particular radionuclides, i.e., alpha emitters and 177Lu. This article will also give insight in the radiation protection issues related to the use of microspheres radiolabeled with either 90Y or 166Ho.

Update on Imaging of Inflammatory Arthritis and Related Disorders.

Arthritis and other rheumatic disorders are very frequent in the general population and responsible for a huge physical and disability burden to affected patients as well as a major cost to the society. Precise evaluation often relies on clinical data only but additional imaging may be required i) for a more objective assessment of the disease status, such as in rheumatoid arthritis (RA) or ankylosing spondyloarthritis (AS), ii) for providing prognostic information and evaluating response to treatment or iii) for establishing diagnosis, in patients with unclear clinical picture, such as polymyalgia rheumatica (PMR) and large-vessel vasculitis (LVV). Besides radiological techniques (x-rays, ultrasound, and MRI), functional and molecular imaging has emerged as a valid tool for this purpose in several disorders. Bone scanning has long been a method of choice but is now more used as a triage tool in patients with unclear complaints, including degenerative disorders (eg osteoarthritis). 18F-FDG-PET/CT (FDG) proved efficient in assessing the extent of the disease and response to treatment in RA and related disorders, and to provide accurate diagnosis in some systemic disorders, including PMR and LVV. Based on glucose metabolism, FDG-PET/CT is able to show increased metabolism in peripheral cells involved in inflammation (eg neutrophils, lymphocytes or monocytes/macrophages) but also in fibroblasts that proliferate in the pannus. The lack of specificity of FDG is a limitation and many alternative tracers were developed at the preclinical stage or applied in the clinics, especially within clinical trials. They include imaging of macrophages using translocator protein (TSPO), folate-receptors or other targets on activated cells. These new tools will undoubtedly become more and more available in the everyday clinical workup of patients with rheumatisms. Finally, it should be kept in mind that a very simple tracer, 18F-fluoride is widely more performant in AS than FDG.

A Theranostic Approach in SIRT: Value of Pre-Therapy Imaging in Treatment Planning.

Selective internal radiation therapy (SIRT) is one of the treatment options for liver tumors. Microspheres labelled with a therapeutic radionuclide (90Y or 166Ho) are injected into the liver artery feeding the tumor(s), usually achieving a high tumor absorbed dose and a high tumor control rate. This treatment adopts a theranostic approach with a mandatory simulation phase, using a surrogate to radioactive microspheres (99mTc-macroaggregated albumin, MAA) or a scout dose of 166Ho microspheres, imaged by SPECT/CT. This pre-therapy imaging aims to evaluate the tumor targeting and detect potential contraindications to SIRT, i.e., digestive extrahepatic uptake or excessive lung shunt. Moreover, the absorbed doses to the tumor(s) and the healthy liver can be estimated and used for planning the therapeutic activity for SIRT optimization. The aim of this review is to evaluate the accuracy of this theranostic approach using pre-therapy imaging for simulating the biodistribution of the microspheres. This review synthesizes the recent publications demonstrating the advantages and limitations of pre-therapy imaging in SIRT, particularly for activity planning.

The role of PET/CT in large vessel vasculitis and related disorders: diagnosis, extent evaluation and assessment of therapy response.

Large vessel vasculitides (LVV) are defined as chronic inflammatory disorders that affect the arteries with two major variants being distinguished: giant cell arteritis (GCA) and Takayasu's arteritis (TAK). These often present with nonspecific constitutional symptoms which makes an accurate diagnosis often challenging. Nevertheless, timely diagnosis is of utmost importance to initiate treatment and to avoid potential life-threatening complications. [18F]FDG-PET/CT is nowadays widely accepted as useful tool to aid in the diagnosis of large vessel vasculitis. However, its role to monitor disease activity and to predict disease relapse during follow-up is less obvious since vascular [18F]FDG uptake can be detected in the absence of clinical or biochemical signs of disease activity. In addition to the two major variants, [18F]FDG-PET/CT has shown promise in (peri-)aortitis and related disorders. This article aims to provide an update on the current knowledge and limitations of [18F]FDG-PET/CT for the diagnosis and assessment of treatment response in LVV. Furthermore, other radiopharmaceuticals targeting key components of the vascular immune system are being discussed which could provide an interesting alternative to image vascular inflammation in LVV.

TCP post-radioembolization and TCP post-EBRT in HCC are similar and can be predicted using the in vitro radiosensitivity.

BACKGROUND: Tumor equivalent uniform dose (EUD) is proposed as a predictor of patient outcome after liver radioembolization (RE) of hepatocellular carcinoma (HCC) and can be evaluated with 90Y-TOF-PET. The aim is to evaluate the correlation between PET-based tumors EUD and the clinical response evaluated with dual molecular tracer (11C-acetate and 18F-FDG) PET/CT post-RE. METHODS: 34 HCC tumors in 22 patients were prospectively evaluated. The metabolic response was characterized by the total lesion metabolism variation (ΔTLM) between baseline and follow-up. This response allowed to compute a tumor control probability (TCP) as a function of the tumor EUD. RESULTS: The absorbed dose response correlation was highly significant (R = 0.72, P < 0.001). With an absorbed dose threshold of 40 Gy, the metabolic response was strongly different in both groups (median response 35% versus 100%, P < 0.001). Post-RE TCP as a function of the EUD was very similar to that observed in external beam radiation therapy (EBRT), with TCP values equal to 0.5 and 0.95 for a EUD of 51 Gy and 100 Gy, respectively. The TCP was perfectly predicted by the Poisson model assuming an inter tumor radiosensitivity variation of 30% around the HCC cell in vitro value. CONCLUSIONS: EUD-based 90Y TOF-PET/CT predicts the metabolic response post-RE in HCC assessed using dual molecular PET tracers and provides a similar TCP curve to that observed in EBRT. In vivo and in vitro HCC radiosensitivities are similar. Both TCPs show that a EUD of 100 Gy is needed to control HCC for the three devices (resin spheres, glass spheres, EBRT). Observed absorbed doses achieving this 100 Gy-EUD ranged from 190 to 1800 Gy!

Optimization of the Clinical Effectiveness of Radioembolization in Hepatocellular Carcinoma with Dosimetry and Patient-Selection Criteria.

Selective internal radiation therapy (SIRT) is part of the treatment strategy for hepatocellular carcinoma (HCC). Strong clinical data demonstrated the effectiveness of this therapy in HCC with a significant improvement in patient outcomes. Recent studies demonstrated a strong correlation between the tumor response and the patient outcome when the tumor-absorbed dose was assessed by nuclear medicine imaging. Dosimetry plays a key role in predicting the clinical response and can be optimized using a personalized method of activity planning (multi-compartmental dosimetry). This paper reviews the main clinical results of SIRT in HCC and emphasizes the central role of dosimetry for improving it effectiveness. Moreover, some patient and tumor characteristics predict a worse outcome, and toxicity related to SIRT treatment of advanced HCC patient selection based on the performance status, liver function, tumor characteristics, and tumor targeting using technetium-99m macro-aggregated albumin scintigraphy can significantly improve the clinical performance of SIRT.

Dual-layer collimator for improved spatial resolution in SPECT with CZT camera: an analytical and Monte Carlo study.

Purpose.Current hole matching pixel detector (HMPD) collimators for SPECT imaging exist in two configurations: one hole per pixel (1HMPD) or four holes per pixel (4HMPD). The aim of this study was to assess the performance of a dual-layer collimator made by stacking up these two collimator types (1H/4HMDP) for low- and medium energy gamma emitters.Method. Analytical equations describing geometrical efficiency and full width at half maximum (FWHM) of the 1H/4HMDP collimator were derived. In addition, a fast dedicated Monte Carlo (MC) code neglecting scattering and designed for the collimator geometry was developed to assess the collimator's point spread function and to simulate planar and SPECT acquisitions.Results.A relative agreement between analytical equations and MC simulations better than 3% was observed for the efficiency and for the FWHM. The length of the two layers was optimized to get the best spatial resolution while keeping the geometrical efficiency equal to that of the 45 mm length 1HMPD collimator. An optimized combination of the 1H/4HMPD configuration with respective hole lengths of 20 and 13 mm has been derived. For source-collimator distances above 5 cm and equal collimator geometrical efficiency, the spatial resolution of this optimal 1H/4HMDP collimator supersedes that of the 45 mm length 1HMPD collimator, and that of the 19.1 mm length 4HMPD collimator. This improvement was observed in simulations of bar phantom planar images and of hot rods phantom SPECT. Remarkably, the spatial resolution was preserved along the whole radial range within the Jaszczak phantom.Conclusion.The 1H/4HMDP collimator is a promising solution for CZT SPECT imaging of low- and medium energy emitters.

Imaging of treatment response and minimal residual disease in multiple myeloma: state of the art WB-MRI and PET/CT.

Bone imaging has been intimately associated with the diagnosis and staging of multiple myeloma (MM) for more than 5 decades, as the presence of bone lesions indicates advanced disease and dictates treatment initiation. The methods used have been evolving, and the historical radiographic skeletal survey has been replaced by whole body CT, whole body MRI (WB-MRI) and [18F]FDG-PET/CT for the detection of bone marrow lesions and less frequent extramedullary plasmacytomas.Beyond diagnosis, imaging methods are expected to provide the clinician with evaluation of the response to treatment. Imaging techniques are consistently challenged as treatments become more and more efficient, inducing profound response, with more subtle residual disease. WB-MRI and FDG-PET/CT are the methods of choice to address these challenges, being able to assess disease progression or response and to detect "minimal" residual disease, providing key prognostic information and guiding necessary change of treatment.This paper provides an up-to-date overview of the WB-MRI and PET/CT techniques, their observations in responsive and progressive disease and their role and limitations in capturing minimal residual disease. It reviews trials assessing these techniques for response evaluation, points out the limited comparisons between both methods and highlights their complementarity with most recent molecular methods (next-generation flow cytometry, next-generation sequencing) to detect minimal residual disease. It underlines the important role of PET/MRI technology as a research tool to compare the effectiveness and complementarity of both methods to address the key clinical questions.

Semi-Quantitative and Quantitative [18F]FDG-PET/CT Indices for Diagnosing Large Vessel Vasculitis: A Critical Review.

To confirm the diagnosis of large vessel vasculitis (LVV) with high accuracy, one of the recommended imaging techniques is [18F]Fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography ([18F]FDG-PET/CT). Visual assessment of [18F]FDG uptake in the arterial wall compared to liver uptake is the mainstay for diagnosing LVV in routine clinical practice. To date, there is no consensus on the preferred semi-quantitative or quantitative parameter for diagnosing LVV. The aim of this review is to critically update the knowledge on the available evidence of semi-quantitative and quantitative [18F]FDG uptake parameters for diagnosing LVV and to provide future directions for methodological standardization and research.

Antireflux catheter improves tumor targeting in liver radioembolization with resin microspheres.

PURPOSE: We aimed to determine whether antireflux (ARC) catheter may result in better tumor targeting in liver radioembolization using 90Y-resin microspheres. METHODS: Patients treated with resin microspheres for hepatocellular carcinoma (HCC) and secondary liver malignancies were retrospectively analyzed. All patients underwent a 99mTc-macroaggregated albumin (99mTc-MAA) single photon emission computed tomography (SPECT) following the planning arteriography with a conventional end-hole catheter. For 90Y-microspheres injection, two groups were defined depending on the type of catheter used: an ARC group (n=38) and a control group treated with a conventional end-hole catheter (n=23). 90Y positron emission tomography computed tomography (PET/CT) was performed after the therapeutic arteriography. The choice of the catheter was not randomized, but left to the choice of the interventional radiologist. 99mTc-MAA SPECT and 90Y PET/CT were co-registered with the baseline imaging to determine a tumor to normal liver ratio (T/NL[MAA or 90Y]) and tumor dose (TD[MAA or 90Y]) for the planning and therapy. RESULTS: Overall, 38 patients (115 lesions) and 23 patients (75 lesions) were analyzed in the ARC and control groups, respectively. In the ARC group, T/NL90Y and TD90Y were significantly higher than T/NLMAA and TDMAA. Median (IQR) T/NL90Y was 2.16 (2.15) versus 1.74 (1.43) for T/NLMAA (p < 0.001). Median (IQR) TD90Y was 90.96 Gy (98.31 Gy) versus 73.72 Gy (63.82 Gy) for TDMAA (p < 0.001). In this group, the differences were highly significant for neuroendocrine metastases (NEM) and HCC and less significant for colorectal metastases (CRM). In the control group, no significant differences were demonstrated. CONCLUSION: The use of an ARC significantly improves tumor deposition in liver radioembolization with resin microspheres.

Comparison of 68Ga-Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography Computed Tomography (PET-CT) and Whole-Body Magnetic Resonance Imaging (WB-MRI) with Diffusion Sequences (DWI) in the Staging of Advanced Prostate Cancer.

BACKGROUND: Prostate specific membrane antigen (PSMA) positron emission tomography computed tomography (PET-CT) and whole-body magnetic resonance imaging (WB-MRI) outperform standard imaging technology for the detection of metastasis in prostate cancer (PCa). There are few direct comparisons between both modalities. This paper compares the diagnostic accuracy of PSMA PET-CT and WB-MRI for the detection of metastasis in PCa. One hundred thirty-four patients with newly diagnosed PCa (n = 81) or biochemical recurrence after curative treatment (n = 53) with high-risk features prospectively underwent PSMA PET-CT and WB-MRI. The diagnostic accuracy of both techniques for lymph node, skeletal and visceral metastases was compared against a best valuable comparator (BVC). Overall, no significant difference was detected between PSMA PET-CT and WB-MRI to identify metastatic patients when considering lymph nodes, skeletal and visceral metastases together (AUC = 0.96 (0.92-0.99) vs. 0.90 (0.85-0.95); p = 0.09). PSMA PET-CT, however, outperformed WB-MRI in the subgroup of patients with newly diagnosed PCa for the detection of lymph node metastases (AUC = 0.96 (0.92-0.99) vs. 0.86 (0.79-0.92); p = 0.0096). In conclusion, PSMA PET-CT outperforms WB-MRI for the detection of nodal metastases in primary staging of PCa.