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.

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.

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.

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.

Renal and Red Marrow Dosimetry in Peptide Receptor Radionuclide Therapy: 20 Years of History and Ahead.

The development of dosimetry and studies in peptide receptor radionuclide therapy (PRRT) over the past two decades are reviewed. Differences in kidney and bone marrow toxicity reported between 90Y, 177Lu and external beam radiotherapy (EBRT) are discussed with regard to the physical properties of these beta emitter radionuclides. The impact of these properties on the response to small and large tumors is also considered. Capacities of the imaging modalities to assess the dosimetry to target tissues are evaluated. Studies published in the past two years that confirm a red marrow uptake in 177Lu-DOTATATE therapy, as already observed 20 years ago in 86Y-DOTATOC PET studies, are analyzed in light of the recent developments in the transferrin transport mechanism. The review enlightens the importance (i) of using state-of-the-art imaging modalities, (ii) of individualizing the activity to be injected with regard to the huge tissue uptake variability observed between patients, (iii) of challenging the currently used but inappropriate blood-based red marrow dosimetry and (iv) of considering individual tandem therapy. Last, a smart individually optimized tandem therapy taking benefit of the bi-orthogonal toxicity-response pattern of 177Lu-DOTATATE and of 90Y-DOTATOC is proposed.

Microspheres Used in Liver Radioembolization: From Conception to Clinical Effects.

Inert microspheres, labeled with several radionuclides, have been developed during the last two decades for the intra-arterial treatment of liver tumors, generally called Selective Intrahepatic radiotherapy (SIRT). The aim is to embolize microspheres into the hepatic capillaries, accessible through the hepatic artery, to deliver high levels of local radiation to primary (such as hepatocarcinoma, HCC) or secondary (metastases from several primary cancers, e.g., colorectal, melanoma, neuro-endocrine tumors) liver tumors. Several types of microspheres were designed as medical devices, using different vehicles (glass, resin, poly-lactic acid) and labeled with different radionuclides, 90Y and 166Ho. The relationship between the microspheres' properties and the internal dosimetry parameters have been well studied over the last decade. This includes data derived from the clinics, but also computational data with various millimetric dosimetry and radiobiology models. The main purpose of this paper is to define the characteristics of these radiolabeled microspheres and explain their association with the microsphere distribution in the tissues and with the clinical efficacy and toxicity. This review focuses on avenues to follow in the future to optimize such particle therapy and benefit to patients.

MRI versus 18F-FDG-PET/CT for detecting bone marrow involvement in multiple myeloma: diagnostic performance and clinical relevance.

PURPOSE: To compare the diagnostic performance of MRI and 18F-FDG-PET/CT in detecting bone marrow involvement (BMI) in patients with multiple myeloma (MM). MATERIALS AND METHODS: This retrospective study was approved by our Institutional Review Board. Two radiologists and two nuclear medicine specialists independently and blindly reviewed 84 pairs of MRI and PET/CT scans obtained in 73 MM patients. Readers assessed the presence and patterns of BMI. The best valuable comparator (BVC) for BMI was established by a panel review of all baseline and follow-up imaging, and biological and pathological information. Intra- and inter-reader agreement and correlation between MRI and PET/CT were assessed using the prevalence-adjusted bias-adjusted kappa (k) coefficient. Diagnostic performance of MRI and PET/CT in detecting BMI was evaluated from ROC characteristics. Association between imaging and biological, pathological, and clinical findings was assessed using Wilcoxon rank-sum and chi-square tests. RESULTS: Intra- and inter-reader agreement was very good for MRI (k = 0.90 [0.81; 1.00] and 0.88 [0.78; 0.98]). Intra- and inter-reader agreement was good for PET/CT (k = 0.80 [0.69; 0.91] and 0.71 [0.56; 0.86]). The sensitivity of MRI to detect BMI (97% [90%; 100%]) was significantly superior to that of PET/CT (76% [64%; 85%]) (p < 0.001). The specificity of MRI (86% [57%; 98%]) was lower than that of PET/CT (93% [66%; 100%]), without reaching statistical significance (p = 0.32). There was a strong correlation between decisions regarding patient management and PET/CT findings (p < 0.001). CONCLUSION: MRI is significantly more sensitive than PET/CT to detect BMI in MM. Patient management is more strongly correlated with PET/CT findings. KEY POINTS: • MRI and PET/CT have very close diagnostic value for the detection of bone marrow involvement in multiple myeloma. • MRI has a significantly higher sensitivity and better reproducibility. • PET/CT findings appear to have a higher impact on clinical decisions.

Clinical efficacy of intranasal drug delivery by nebulization in chronic rhinosinusitis: a systematic review.

BACKGROUND: Treatment of chronic rhinosinusitis (CRS) aims to treat the underlying inflammation or infection. Although the optimal modality of administration remains controversial, inhalation route is usually preferred. The aim of this systematic review was to summarize the efficacy of intranasal corticoisteroids or antibiotics delivery by nebulization on symptoms, histology, endoscopy scores, nasal obstruction, clinical outcomes and quality of life in CRS. METHOD: This systematic review followed the PRISMA guidelines. Randomized controlled, comparative and cohort studies evaluating effects of treatment by nebulization in sinusitis were identified and reviewed from two databases (PubMed and Scopus). Two reviewers independently assessed study quality and reviewed the selected studies. RESULTS: 600 references were retrieved and 12 studies evaluating 377 patients were included in the systematic review. Different devices were used. Efficacy of nasal delivery by nebulization was systematically observed on symptoms and size of polyps and frequently on inflammatory parameters in all studies. The presence of polyps improved the efficacy of the nebulization. This way of delivery appears not convincing regarding antibiotics. Few side effects were noted in the retrieved studies and only for nebulized antibiotics. CONCLUSIONS: This systematic review highlighted that based on the present literature nebulization is not better than nasal spray to the delivery of corticosteroids due to the positive results on symptoms, endoscopic appearance and histological outcomes. For antibiotics delivery, the nebulization is not of added value.

Use of imaging techniques in large vessel vasculitis and related conditions.

Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are large vessel vasculitis (LVV) primarily affecting the aorta and its major branches, mainly differentiated by the onset age (>50 years GCA and <40 years TA). In addition, temporal artery involvement and polymyalgia rheumatica are typical features of GCA, but not TA. Imaging techniques are required to secure the diagnosis of large-vessel vasculitides, and to monitor the disease course. Both morphological and metabolic imaging are involved. Morphological imaging is represented mainly by computerized tomography (CT), CT angiography, magnetic resonance (MR), MR angiography, color-Doppler sonography (CDS) and high-resolution CDS. Metabolic aspects of inflammatory process in LVV can be well studied by positron emission tomography/computed tomography with [18F]deoxyglucose ([18F]FDG PET/CT). It has an important increasing role in diagnosis, extent assessment and disease activity and therapy response evaluation. In the near future the concomitant development of increasingly powerful PET/CT scanners, of new radiopharmaceuticals more specific for inflammation, and of new PET/MRI hybrid scanners probably will lead to a further new step forward in the diagnosis and clinical management of LVV.

SPECT-CT Comparison of Lung Deposition using a System combining a Vibrating-mesh Nebulizer with a Valved Holding Chamber and a Conventional Jet Nebulizer: a Randomized Cross-over Study.

PURPOSE: To compare in vivo the total and regional pulmonary deposition of aerosol particles generated by a new system combining a vibrating-mesh nebulizer with a specific valved holding chamber and constant-output jet nebulizer connected to a corrugated tube. METHODS: Cross-over study comparing aerosol delivery to the lungs using two nebulizers in 6 healthy male subjects: a vibrating-mesh nebulizer combined with a valved holding chamber (Aerogen Ultra®, Aerogen Ltd., Galway, Ireland) and a jet nebulizer connected to a corrugated tube (Opti-Mist Plus Nebulizer®, ConvaTec, Bridgewater, NJ). Nebulizers were filled with diethylenetriaminepentaacetic acid labelled with technetium-99 m (99mTc-DTPA, 2 mCi/4 mL). Pulmonary deposition of 99mTc-DTPA was measured by single-photon emission computed tomography combined with a low dose CT-scan (SPECT-CT). RESULTS: Pulmonary aerosol deposition from SPECT-CT analysis was six times increased with the vibrating-mesh nebulizer as compared to the jet nebulizer (34.1 ± 6.0% versus 5.2 ± 1.1%, p < 0.001). However, aerosol penetration expressed as the three-dimensional normalized ratio of the outer and the inner regions of the lungs was similar between both nebulizers. CONCLUSIONS: This study demonstrated the high superiority of the new system combining a vibrating-mesh nebulizer with a valved holding chamber to deliver nebulized particles into the lungs as comparted to a constant-output jet nebulizer with a corrugated tube.

Aerosol delivery during invasive mechanical ventilation: a systematic review.

BACKGROUND: This systematic review aimed to assess inhaled drug delivery in mechanically ventilated patients or in animal models. Whole lung and regional deposition and the impact of the ventilator circuit, the artificial airways and the administration technique for aerosol delivery were analyzed. METHODS: In vivo studies assessing lung deposition during invasive mechanical ventilation were selected based on a systematic search among four databases. Two investigators independently assessed the eligibility and the risk of bias. RESULTS: Twenty-six clinical and ten experimental studies were included. Between 30% and 43% of nominal drug dose was lost to the circuit in ventilated patients. Whole lung deposition of up to 16% and 38% of nominal dose (proportion of drug charged in the device) were reported with nebulizers and metered-dose inhalers, respectively. A penetration index inferior to 1 observed in scintigraphic studies indicated major proximal deposition. However, substantial concentrations of antibiotics were measured in the epithelial lining fluid (887 (406-12,819) µg/mL of amikacin) of infected patients and in sub-pleural specimens (e.g., 197 µg/g of amikacin) dissected from infected piglets, suggesting a significant distal deposition. The administration technique varied among studies and may explain a degree of the variability of deposition that was observed. CONCLUSIONS: Lung deposition was lower than 20% of nominal dose delivered with nebulizers and mostly occurred in proximal airways. Further studies are needed to link substantial concentrations of antibiotics in infected pulmonary fluids to pulmonary deposition. The administration technique with nebulizers should be improved in ventilated patients in order to ensure an efficient but safe, feasible and reproducible technique.

Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity.

Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut-brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence.

Does the site of platelet sequestration predict the response to splenectomy in adult patients with immune thrombocytopenic purpura?

Splenectomy is the only potentially curative treatment for chronic immune thrombocytopenic purpura (ITP) in adults. However, one-third of the patients relapse without predictive factors identified. We evaluate the predictive value of the site of platelet sequestration on the response to splenectomy in patients with ITP. Eighty-two consecutive patients with ITP treated by splenectomy between 1992 and 2013 were retrospectively reviewed. Platelet sequestration site was studied by (111)Indium-oxinate-labeled platelets in 93% of patients. Response to splenectomy was defined at last follow-up as: complete response (CR) for platelet count (PC) ≥100 × 10(9)/L, response (R) for PC≥30 × 10(9)/L and <100 × 10(9)/L with absence of bleeding, no response (NR) for PC<30 × 10(3)/L or significant bleeding. Laparoscopic splenectomy was performed in 81 patients (conversion rate of 16%), and open approach in one patient. Median follow-up was 57 months (range, 1-235). Platelet sequestration study was performed in 93% of patients: 50 patients (61%) exhibited splenic sequestration, 9 (11%) hepatic sequestration and 14 patients (17%) mixed sequestration. CR was obtained in 72% of patients, R in 25% and NR in 4% (two with splenic sequestration, one with hepatic sequestration). Preoperative PC, age at diagnosis, hepatic sequestration and male gender were significant for predicting CR in univariate analysis, but only age (HR = 1.025 by one-year increase, 95% CI [1.004-1.047], p = 0.020) and pre-operative PC (HR = 0.112 for > 100 versus <=100, 95% CI [0.025-0.493], p = 0.004) were significant predictors of recurrence-free survival in multivariate analysis. Response to splenectomy was independent of the site of platelet sequestration in patients with ITP. Pre-operative platelet sequestration study in these patients cannot be recommended.

Quantification of osmotic water transport in vivo using fluorescent albumin.

Osmotic water transport across the peritoneal membrane is applied during peritoneal dialysis to remove the excess water accumulated in patients with end-stage renal disease. The discovery of aquaporin water channels and the generation of transgenic animals have stressed the need for novel and accurate methods to unravel molecular mechanisms of water permeability in vivo. Here, we describe the use of fluorescently labeled albumin as a reliable indicator of osmotic water transport across the peritoneal membrane in a well-established mouse model of peritoneal dialysis. After detailed evaluation of intraperitoneal tracer mass kinetics, the technique was validated against direct volumetry, considered as the gold standard. The pH-insensitive dye Alexa Fluor 555-albumin was applied to quantify osmotic water transport across the mouse peritoneal membrane resulting from modulating dialysate osmolality and genetic silencing of the water channel aquaporin-1 (AQP1). Quantification of osmotic water transport using Alexa Fluor 555-albumin closely correlated with direct volumetry and with estimations based on radioiodinated ((125)I) serum albumin (RISA). The low intraperitoneal pressure probably accounts for the negligible disappearance of the tracer from the peritoneal cavity in this model. Taken together, these data demonstrate the appropriateness of pH-insensitive Alexa Fluor 555-albumin as a practical and reliable intraperitoneal volume tracer to quantify osmotic water transport in vivo.

One-step TNM staging of high-risk prostate cancer using magnetic resonance imaging (MRI): toward an upfront simplified "all-in-one" imaging approach?

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) is the standard for local prostate cancer (PCa) staging. Whole-body MRI (wbMRI) has shown capabilities for metastatic screening. This study assesses the feasibility and value of an all-in-one AJCC TNM staging of PCa during a unique MRI session combining mpMRI and wbMRI. METHODS: Thirty consecutive patients with "high-risk" PCa prospectively underwent mpMRI of the prostate and wbMRI, in addition to (99m) Tc bone scan (BS), completed with standard X-rays (±TXR) and contrast enhanced CT for distant staging. For the statistical analysis, a "best valuable comparator" (BVC) combining a panel review of all available baseline and follow-up imaging, biological, and clinical data was used to adjudicate lymph node and bone metastatic status. RESULTS: Prostate mpMRI was analyzed using ESUR guidelines. Sensitivity of BS ± TXR combined with CT and of wbMRI for detecting metastases (bones or nodes) was 85% and 100%, respectively, and specificity was 88% and 100%, respectively. For the overall staging of the patients as being either N0M0 or having disease extension beyond the prostate, wbMRI was superior to the combination of BS and CT (improvement in all ROC characteristics and of AUC by 13.6% (95% CI: +0.7% to +26.5%, P = 0.039)). The main limitation is the limited number of patients. CONCLUSIONS: AJCC M and N staging using wbMRI is feasible during the same imaging session as mpMRI performed for T staging, in less then one hour. wbMRI outperforms BS ± TXR and abdomino-pelvic CT work up for discriminating subsets of patients with or without distant spread of the cancer.

Validation of anatomical models to study aerosol deposition in human nasal cavities.

PURPOSE: Intranasal deposition of aerosols is often studied using in vitro nasal cavity models. However, the relevance of these models to predict in vivo human deposition has not been validated. This study compared in vivo nasal aerosol deposition and in vitro deposition in a human plastinated head model (NC1) and its replica constructed from CT-scan (NC2). METHODS: Two nebulizers (Atomisor Sonique® and Easynose®) were used to administer a 5.6 µm aerosol of (99m)Tc-DTPA to seven healthy volunteers and to the nasal models. Aerosol deposition was quantified by γ-scintigraphy in the nasal, upper nasal cavity and maxillary sinus (MS) regions. The distribution of aerosol deposition was determined along three nasal cavity axes (x, y and z). RESULTS: There was no significant difference regarding aerosol deposition between the volunteers and NC1. Aerosol deposition was significantly lower in NC2 than in volunteers regarding nasal region (p < 0.05) but was similar for the upper nasal cavity and MS regions. Mean aerosol distribution for NC1 came within the standard deviation (SD) of in vivo distribution, whereas that of NC2 was outside the in vivo SD for x and y axes. CONCLUSIONS: In conclusion, nasal models can be used to predict aerosol deposition produced by nebulizers, but their performance depends on their design.