Prediction of Acute Radiation-Induced Lung Toxicity After Stereotactic Body Radiation Therapy Using Dose-Volume Parameters From Functional Mapping on Gallium 68 Perfusion Positron Emission Tomography/Computed Tomography.

PURPOSE: The aim of this work was to compare anatomic and functional dose-volume parameters as predictors of acute radiation-induced lung toxicity (RILT) in patients with lung tumors treated with stereotactic body radiation therapy. METHODS AND MATERIALS: Fifty-nine patients treated with stereotactic body radiation therapy were prospectively included. All patients underwent gallium 68 lung perfusion positron emission tomography (PET)/computed tomography (CT) imaging before treatment. Mean lung dose (MLD) and volumes receiving x Gy (VxGy, 5-30 Gy) were calculated in 5 lung volumes: the conventional anatomic volume (AV) delineated on CT images, 3 lung functional volumes (FVs) defined on lung perfusion PET imaging (FV50%, FV70%, and FV90%; ie, the minimal volume containing 50%, 70%, and 90% of the total activity within the AV), and a low FV (LFV; LFV = AV - FV90%). The primary endpoint of this analysis was grade ≥2 acute RILT at 3 months as assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Dose-volume parameters in patients with and without acute RILT were compared. Receiver operating characteristic curves assessing the ability of dose-volume parameters to discriminate between patients with and without acute RILT were generated, and area under the curve (AUC) values were calculated. RESULTS: Of the 59 patients, 10 (17%) had grade ≥2 acute RILT. The MLD and the VxGy in the AV and LFV were not statistically different between patients with and without acute RILT (P > .05). All functional parameters were significantly higher in acute RILT patients (P < .05). AUC values (95% CI) for MLD AV, LFV, FV50%, FV70%, and FV90% were 0.66 (0.46-0.85), 0.60 (0.39-0.80), 0.77 (0.63-0.91), 0.77 (0.64-0.91), and 0.75 (0.58-0.91), respectively. AUC values for V20Gy AV, LFV, FV50%, FV70%, and FV90% were 0.65 (0.44-0.87), 0.64 (0.46-0.83), 0.82 (0.69-0.95), 0.81 (0.67-0.96), and 0.75 (0.57-0.94), respectively. CONCLUSIONS: The predictive value of PET perfusion-based functional parameters outperforms the standard CT-based dose-volume parameters for the risk of grade ≥2 acute RILT. Functional parameters could be useful for guiding radiation therapy planning and reducing the risk of acute RILT.

Scintigraphic Diagnosis of Acute Pulmonary Embolism: From Basics to Best Practices.

In this article the technique, interpretation, and diagnostic performance of scintigraphy for the diagnosis of acute pulmonary embolism (PE) are reviewed. Lung scintigraphy has stood the test of time as a reliable and validated examination for the determination of PE. Ventilation/perfusion (V/Q) lung scintigraphy assesses the functional consequences of the clot on its downstream vascular bed in conjunction with the underlying ventilatory status of the affected lung region, in contrast to CT pulmonary angiography (CTPA), which visualizes presence of the clot within affected vessels. Most-commonly used ventilation radiopharmaceuticals are Technetium-99m labeled aerosols (such as 99mTechnetium-DTPA), or ultrafine particle suspensions (99mTc-Technegas) which reach the distal lung in proportion to regional distribution of ventilation. Perfusion images are obtained after intravenous administration 99mTc-labeled macro-aggregated albumin particles which lodge in the distal pulmonary capillaries. Both planar and tomographic methods of imaging, each favored in different geographical regions, will be described. Guidelines for interpretation of scintigraphy have been issues by both the Society of Nuclear Medicine and Molecular Imaging, and by the European Association of Nuclear Medicine. Breast tissue is particularly radiosensitive during pregnancy due to its highly proliferative state and many guidelines recommend use of lung scintigraphy rather than CTPA in this population. Several maneuvers are available in order to further reduce radiation exposure including reducing radiopharmaceutical dosages or omitting ventilation altogether, functionally converting the study to a low-dose screening examination; if perfusion defects are present, further testing is necessary. Several groups have also performed perfusion-only studies during the COVID epidemic in order to reduce risk of respiratory contagion. In patients where perfusion defects are present, further testing is again necessary to avoid false-positive results. Improved availability of personal protective equipment, and reduced risk of serious infection, have rendered this maneuver moot in most practices. First introduced 60 years ago, subsequent advances in radiopharmaceutical development and imaging methods have positioned lung scintigraphy to continue to play an important clinical and research role in the diagnosis of acute PE.

New Automated Method for Lung Functional Volumes Delineation with Lung Perfusion PET/CT Imaging.

BACKGROUND: Gallium-68 lung perfusion PET/CT is an emerging imaging modality for the assessment of regional lung function, especially to optimise radiotherapy (RT) planning. A key step of lung functional avoidance RT is the delineation of lung functional volumes (LFVs) to be integrated into radiation plans. However, there is currently no consistent and reproducible delineation method for LFVs. The aim of this study was to develop and evaluate an automated delineation threshold method based on total lung function for LFVs delineation with Gallium-68 MAA lung PET/CT imaging. MATERIAL AND METHOD: Patients prospectively enrolled in the PEGASUS trial-a pilot study assessing the feasibility of lung functional avoidance using perfusion PET/CT imaging for lung stereotactic body radiotherapy (SBRT) of primary or secondary lesion-were analysed. Patients underwent lung perfusion MAA-68Ga PET/CT imaging and pulmonary function tests (PFTs) as part of pre-treatment evaluation. LFVs were delineated using two methods: the commonly used relative to the maximal pixel value threshold method (pmax threshold method, X%pmax volumes) and a new approach based on a relative to whole lung function threshold method (WLF threshold method, FVX% volumes) using a dedicated iterative algorithm. For both methods, LFVs were expressed in terms of % of the anatomical lung volume (AV) and of % of the total lung activity. Functional volumes were compared for patients with normal PFTs and pre-existing airway disease. RESULTS: 60 patients were analysed. Among the 48 patients who had PFTs, 31 (65%) had pre-existing lung disease. The pmax and WLF threshold methods clearly provided different functional volumes with a wide range of relative lung function for a given pmax volume, and conversely, a wide range of corresponding pmax values for a given WLF volume. The WLF threshold method provided more reliable and consistent volumes with much lower dispersion of LFVs as compared to the pmax method, especially in patients with normal PFTs. CONCLUSIONS: We developed a relative to whole lung function threshold segmentation method to delineate lung functional volumes on perfusion PET/CT imaging. The automated algorithm allows for reproducible contouring. This new approach, relatively unaffected by the presence of hot spots, provides reliable and consistent functional volumes, and is clinically meaningful for clinicians.

A Feasibility Study of Functional Lung Volume Preservation during Stereotactic Body Radiotherapy Guided by Gallium-68 Perfusion PET/CT.

The aim of this study was to assess the feasibility of sparing functional lung areas by integration of pulmonary functional mapping guided by 68Ga-perfusion PET/CT imaging in lung SBRT planification. Sixty patients that planned to receive SBRT for primary or secondary lung tumors were prospectively enrolled. Lung functional volumes were defined as the minimal volume containing 50% (FV50%), 70% (FV70%) and 90% (FV90%) of the total activity within the anatomical volume. All patients had a treatment planning carried out in 2 stages: an anatomical planning blinded to the PET results and then a functional planning respecting the standard constraints but also incorporating "lung functional volume" constraints. The mean lung dose (MLD) in functional volumes and the percentage of lung volumes receiving xGy (VxGy) within the lung functional volumes using both plans were calculated and compared. SBRT planning optimized to spare lung functional regions led to a significant reduction (p < 0.0001) of the MLD and V5 to V20 Gy in all functional volumes. Median relative difference of the MLD in the FV50%, FV70% and FV90% was -8.0% (-43.0 to 1.2%), -7.1% (-34.3 to 1.2%) and -5.7% (-22.3 to 4.4%), respectively. Median relative differences for VxGy ranged from -12.5% to -9.2% in the FV50%, -11.3% to -7.2% in the FV70% and -8.0% to -5.3% in the FV90%. This study shows the feasibility of significantly decreasing the doses delivered to the lung functional volumes using 68Ga-perfusion PET/CT while still respecting target volume coverage and doses to other organs at risk.

Lung Stereotactic Body Radiation Therapy in a Patient with Severe Lung Function Impairment Allowed by Gallium-68 Perfusion PET/CT Imaging: A Case Report.

Lung stereotactic body radiotherapy (SBRT) is increasingly proposed, especially for patients with poor lung function who are not eligible for surgery. However, radiation-induced lung injury remains a significant treatment-related adverse event in these patients. Moreover, for patients with very severe COPD, we have very few data about the safety of SBRT for lung cancer. We present the case of a female with very severe chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in one second (FEV1) of 0.23 L (11%), for whom a localized lung tumor was found. Lung SBRT was the only possible treatment. It was allowed and safely performed, based on a pre-therapeutic evaluation of regional lung function with Gallium-68 perfusion lung positron emission tomography combined with computed tomography (PET/CT). This is the first case report to highlight the potential use of a Gallium-68 perfusion PET/CT in order to safely select patients with very severe COPD who can benefit from SBRT.

Residual pulmonary vascular obstruction and recurrence after acute pulmonary embolism: a systematic review and meta-analysis of individual participant data.

We aimed to assess the relationship between residual pulmonary vascular obstruction (RPVO) on planar lung scan after completion of at least 3 months of anticoagulant therapy for acute pulmonary embolism (PE) and the risk of recurrent venous thromboembolism (VTE) or death due to PE one year after treatment discontinuation. The systematic review was registered with the International Prospective Registry of Systematic Reviews (PROSPERO: CRD42017081080). The primary outcome measure was to generate a pooled estimate of the rate of recurrent VTE at one year in patient with RPVO diagnosed on planar lung scan after discontinuation of at least 3 months of anticoagulant treatment for an acute PE. Individual data were obtained for 809 patients. RPVO (ie, obstruction >0%) was found in 407 patients (50.3%) after a median of 6.6 months of anticoagulant therapy for a first acute PE. Recurrent VTE or death due to PE occurred in 114 patients (14.1%), for an annual risk of 6.4% (95% confidence interval, 4.7%-8.6%). Out of the 114 recurrent events, 63 occurred within one year after discontinuation of anticoagulant therapy corresponding to a risk of 8.1% (6.4%-9.8%) at 1 year. The risk of recurrent VTE at one year was 5.8% (4.4-7.2) in participants with RPVO <5%, vs 11.7% (9.5-13.8) in participants with RPVO ≥5%. RPVO is a significant predictor of the risk of recurrent venous thromboembolism. However, the risk of recurrent events remains too high in patients without residual perfusion defect for it to be used as a stand-alone test to decide on anticoagulation discontinuation.

PSMA-11 PET/CT for Detection of Recurrent Prostate Cancer in Patients With Negative Choline PET/CT.

INTRODUCTION: Prostate adenocarcinoma (CaP) is the leading cancer in men. After curative treatment, from 27% to 53% of patients will experience biochemical recurrence (BR). With the development of focal therapies, precise early identification of recurrence's sites is of utmost importance in order to deliver individualized treatment on positive lesions. The aim of this study was to assess the detection rate (DR) of 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) in selected patients with prostate cancer BR and recent negative 18F-choline PET/CT. PATIENTS AND METHODS: We performed a retrospective analysis including all patients with CaP referred for BR with a negative 18F-choline PET/CT, and who underwent 68Ga-PSMA-11 PET/CT between October, 2018 and December, 2019. The overall DR of 68Ga-PSMA-11 PET/CT was calculated, and described according to BR characteristics especially PSA levels and velocity. Patients were followed up for at least 1 year. Patient management following 68Ga-PSMA-11 PET/CT and PSA levels evolution after treatment were also recorded. RESULTS: One hundred fifty-nine patients comprising 164 examinations were analyzed. The overall DR of 68Ga-PSMA-11 PET/CT for BR was 65.9% (95CI, 58.6-73.1). The DR was 52.5% (95CI, 39.9-65.0), 70.6% (95CI, 55.3-85.9), 70.4% (95CI, 53.1-87.6), and 78.6% (95CI, 66.2-91.0) for PSA levels between 0.2 and 0.49 ng/mL, 0.5 to 0.99 ng/mL, 1 to 1.99 ng/mL and PSA ≥ 2 ng/mL, respectively. The DR was 70.7% (95CI, 59.0-82.4) with a PSA doubling time (PSA-DT) ≤6 months and 65.2% (95CI, 55.5-74.9) with a PSA-DT >6 months. Around 3/4 of patients (75.9%) with a positive 68Ga-PSMA-11 PET/CT initiated treatment, including surgery (2.4%), stereotactic radiotherapy ± androgen deprivation therapy (ADT) (22%) or external conformational radiotherapy ± ADT (46.3%). Patient management changed in 43 cases (39.8%). CONCLUSION: Our study confirmed the ability of 68Ga-PSMA-11 PET/CT to detect occult biochemical recurrence, even in a selected population of CaP patients with negative 18F-choline PET/CT, even at low PSA levels.

Ventilation Scintigraphy With Radiolabeled Carbon Nanoparticulate Aerosol (Technegas): State-of-the-Art Review and Diagnostic Applications to Pulmonary Embolism During COVID-19 Pandemic.

ABSTRACT: Invented and first approved for clinical use in Australia 36 years ago, Technegas is the technology that enabled ventilation scintigraphy with 99m Tc-labeled carbon nanoparticles ( 99m Tc-CNP). The US Food and Drug Administration (FDA) has considered this technology for more than 30 years but only now is getting close to approving it. Meanwhile, more than 4.4 million patients benefited from this technology in 64 countries worldwide. The primary application of 99m Tc-CNP ventilation imaging is the diagnostic evaluation for suspicion of pulmonary embolism using ventilation-perfusion quotient (V/Q) imaging. Because of 99m Tc-CNP's long pulmonary residence, tomographic imaging emerged as the preferred V/Q methodology. The FDA-approved ventilation imaging agents are primarily suitable for planar imaging, which is less sensitive. After the FDA approval of Technegas, the US practice will likely shift to tomographic V/Q. The 99m Tc-CNP use is of particular interest in the COVID-19 pandemic because it offers an option of a dry radioaerosol that takes approximately only 3 to 5 tidal breaths, allowing the shortest exposure to and contact with possibly infected patients. Indeed, countries where 99m Tc-CNP was approved for clinical use continued using it throughout the COVID-19 pandemic without known negative viral transmission consequences. Conversely, the ventilation imaging was halted in most US facilities from the beginning of the pandemic. This review is intended to familiarize the US clinical nuclear medicine community with the basic science of 99m Tc-CNP ventilation imaging and its clinical applications, including common artifacts and interpretation criteria for tomographic V/Q imaging for pulmonary embolism.

Radiation exposure to nuclear medicine technologists performing a V/Q PET: Comparison with conventional V/Q scintigraphy, [18F]FDG PET and [68Ga]Ga DOTATOC PET procedures.

Introduction: Ventilation/Perfusion (V/Q) PET/CT is an emerging imaging modality for regional lung function evaluation. The same carrier molecules as conventional V/Q scintigraphy are used but they are radiolabelled with gallium-68 (68Ga) instead of technetium-99m (99mTc). A recurrent concern regarding V/Q PET imaging is the radiation dose to the healthcare workers. The aim of this study was to evaluate the total effective dose and the finger dose received by the technologist when performing a V/Q PET procedure, and to compare them with the radiations doses received with conventional V/Q scintigraphy, FDG PET and Ga DOTATOC PET procedures. Materials and methods: The whole body dose measurement was performed 10 times for each of the evaluated procedures using an electronic personal dosimeter (ED). For V/Q PET and V/Q scintigraphy procedures, ventilation and perfusion stages were separately evaluated. Internal exposure was measured for ventilation procedures. Finger dose measurements were performed 5 times for each of the PET procedures using Thermoluminescence (TL) pellets. Results: The technologist effective dose when performing a V/Q PET procedure was 2.83 ± 0.67 µSv, as compared with 1.16 ± 0.34 µSv for conventional V/Q scintigraphy, 2.13 ± 0.77 µSv for [68Ga]Ga-DOTATOC, and 2.86 ± 1.79 µSv for FDG PET procedures, respectively. The finger dose for the V/Q PET procedure was similar to the dose for a [68Ga]Ga-DOTATOC scan (0.35 mSv and 0.32 mSv, respectively). Conclusion: The technologist total effective dose for a V/Q PET procedure is ~2.4 higher than the dose for a conventional V/Q scintigraphy, but in the same range than the radiation exposure when performing common PET procedures, both in terms of total effective dose or finger dose. These results should be reassuring for the healthcare workers performing a V/Q PET procedure.

Quantification of the pulmonary vascular obstruction index on ventilation/perfusion lung scintigraphy: Comparison of a segmental visual scoring to the Meyer score.

Introduction: Quantifying the pulmonary vascular obstruction index (PVOI) is essential for the management of patients with pulmonary embolism or chronic thromboembolic pulmonary hypertension (CTEPH). The reference method for quantifying the PVOI with planar lung ventilation/perfusion (V/Q) scintigraphy is the Meyer score, which was validated using pulmonary angiography as a reference standard. However, it is complex to use in daily practice. In contrast, a rapid and fast quantification method consists in estimating the PVOI based on the number of segmental perfusion defects. However, the accuracy of this method has never been evaluated. In this study, we aimed to compare PVOI quantification on planar V/Q scintigraphy assessed by a segmental visual scoring (SVS) to the Meyer score. Materials and methods: The eligible study population consisted of consecutive patients who underwent planar V/Q scan for CTEPH screening. A central review was performed by three nuclear medicine physicians. PVOI was assessed by summing the number of segmental perfusion defects or equivalent (2 sub-segments = 1 segment = 5%) and by Meyer's method. The two interpretations were performed 6 months apart. A Spearman rank correlation coefficient was calculated to evaluate correlation between the two measurement methods. An intra-class correlation (ICC) was calculated to assess agreement. A Bland et Altman plot analysis was used to evaluate agreement between the two measurements. Results: A total of 226 V/Q scans were interpreted. Spearman rank correlation coefficient between SVS and Meyer was 0.963 (95%CI 0.952-0.971) for mismatched perfusion defects and 0.963 (95%CI 0.953-0.972) for perfusion defects regardless of ventilation. Intra-class correlation (ICC) for agreement was 0.978 (95%CI 0.972-0.983) for mismatched perfusion defects and 0.968 (95%CI 0.959-0.976) for perfusion defects regardless of ventilation. In Bland & Altmann analysis, the mean difference between the SVS method and the Meyer score was 0.42 and 0.61 for the mismatched or matched evaluation, respectively. Conclusion: Our study shows a high correlation, and low differences in PVOI quantification when using a segmental visual scoring (SVS) as compared to the Meyer score. The SVS has the great advantage to be easy and rapid to apply in daily practice.

Frequency and predictors for chronic thromboembolic pulmonary hypertension after a first unprovoked pulmonary embolism: Results from PADIS studies.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication of a pulmonary embolism (PE) whose incidence and predictors are not precisely determined. OBJECTIVE: To determine the frequency and predictors for CTEPH after a first unprovoked PE. PATIENTS/METHODS: In a randomized trial comparing an additional 18-month warfarin versus placebo in patients after a first unprovoked PE initially treated with vitamin K antagonist for 6 months, we applied recommended CTEPH screening strategies through an 8-year follow-up to determine cumulative incidence of CTEPH. CTEPH predictors were estimated using Cox models. Pulmonary vascular obstruction (PVO) and systolic pulmonary arterial pressure (sPAP) at PE diagnosis and 6 months were studied by receiver operating curves analysis. All CTEPH cases and whether they were incident or prevalent were adjudicated. RESULTS: During a median follow-up of 8.7 years, nine CTEPH cases were diagnosed among 371 patients, with a cumulative incidence of 2.8% (95% confidence interval [CI] 0.95-4.64), and of 1.31% (95% CI 0.01-2.60) after exclusion of five cases adjudicated as prevalent. At PE diagnosis, PVO > 45% and sPAP > 56 mmHg were associated with CTEPH with a hazard ratio (HR) of 33.00 (95% CI 1.64-667.00, p = .02) and 12.50 (95% CI 2.10-74.80, p < .01), respectively. Age > 65 years, lupus anticoagulant antibodies and non-O blood groups were also predictive of CTEPH. PVO > 14% and sPAP > 34 mmHg at 6 months were associated with CTEPH (HR 63.90 [95% CI 3.11-1310.00, p < .01]and HR 17.2 [95% CI 2.75-108, p < .01]). CONCLUSION: After a first unprovoked PE, CTEPH cumulative incidence was 2.8% during an 8-year follow-up. PVO and sPAP at PE diagnosis and at 6 months were the main predictors for CTEPH diagnosis.

Radiopharmaceutical Labelling for Lung Ventilation/Perfusion PET/CT Imaging: A Review of Production and Optimization Processes for Clinical Use.

Lung ventilation/perfusion (V/Q) positron emission tomography-computed tomography (PET/CT) is a promising imaging modality for regional lung function assessment. The same carrier molecules as a conventional V/Q scan (i.e., carbon nanoparticles for ventilation and macro aggregated albumin particles for perfusion) are used, but they are labeled with gallium-68 (68Ga) instead of technetium-99m (99mTc). For both radiopharmaceuticals, various production processes have been proposed. This article discusses the challenges associated with the transition from 99mTc- to 68Ga-labelled radiopharmaceuticals. The various production and optimization processes for both radiopharmaceuticals are reviewed and discussed for optimal clinical use.

Functional Alterations Due to COVID-19 Lung Lesions-Lessons From a Multicenter V/Q Scan-Based Registry.

PURPOSE: In coronavirus disease 2019 (COVID-19) patients, clinical manifestations as well as chest CT lesions are variable. Lung scintigraphy allows to assess and compare the regional distribution of ventilation and perfusion throughout the lungs. Our main objective was to describe ventilation and perfusion injury by type of chest CT lesions of COVID-19 infection using V/Q SPECT/CT imaging. PATIENTS AND METHODS: We explored a national registry including V/Q SPECT/CT performed during a proven acute SARS-CoV-2 infection. Chest CT findings of COVID-19 disease were classified in 3 elementary lesions: ground-glass opacities, crazy-paving (CP), and consolidation. For each type of chest CT lesions, a semiquantitative evaluation of ventilation and perfusion was visually performed using a 5-point scale score (0 = normal to 4 = absent function). RESULTS: V/Q SPECT/CT was performed in 145 patients recruited in 9 nuclear medicine departments. Parenchymal lesions were visible in 126 patients (86.9%). Ground-glass opacities were visible in 33 patients (22.8%) and were responsible for minimal perfusion impairment (perfusion score [mean ± SD], 0.9 ± 0.6) and moderate ventilation impairment (ventilation score, 1.7 ± 1); CP was visible in 43 patients (29.7%) and caused moderate perfusion impairment (2.1 ± 1.1) and moderate-to-severe ventilation impairment (2.5 ± 1.1); consolidation was visible in 89 patients (61.4%) and was associated with moderate perfusion impairment (2.1 ± 1) and severe ventilation impairment (3.0 ± 0.9). CONCLUSIONS: In COVID-19 patients assessed with V/Q SPECT/CT, a large proportion demonstrated parenchymal lung lesions on CT, responsible for ventilation and perfusion injury. COVID-19-related pulmonary lesions were, in order of frequency and functional impairment, consolidations, CP, and ground-glass opacity, with typically a reverse mismatched or matched pattern.

Quantitative assessment of ventilation-perfusion relationships with gallium-68 positron emission tomography/computed tomography imaging in lung cancer patients.

Pulmonary functional imaging has demonstrated potential to improve thoracic radiotherapy. The purpose of this study was twofold: 1) to quantify ventilation/perfusion relationships in lung cancer patients using a new functional imaging approach, gallium-68 (68Ga)-positron emission tomography/computed tomography (PET/CT); and 2) to compare ventilation/perfusion matching with diffusing capacity of the lung for carbon monoxide (DLCO). Voxel-wise correlations between ventilation and perfusion varied widely among 19 patients (range: 0.26-0.88). 68Ga-PET/CT-measured percent gas exchanging lung volume was moderately correlated with DLCO (≤0.59). Our findings suggested that 68Ga-PET/CT ventilation/perfusion imaging provided complementary information and a reasonable surrogate for gas exchange in lung cancer patients.

Lung Ventilation/Perfusion Scintigraphy for the Screening of Chronic Thromboembolic Pulmonary Hypertension (CTEPH): Which Criteria to Use?

Objective: The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is a major challenge as it is a curable cause of pulmonary hypertension (PH). Ventilation/Perfusion (V/Q) lung scintigraphy is the imaging modality of choice for the screening of CTEPH. However, there is no consensus on the criteria to use for interpretation. The aim of this study was to assess the accuracy of various interpretation criteria of planar V/Q scintigraphy for the screening of CTEPH in patients with PH. Methods: The eligible study population consisted of consecutive patients with newly diagnosed PH in the Brest University Hospital, France. Final diagnosis (CTEPH or non-CTEPH) was established in a referential center on the management of PH, based on the ESC/ERS guidelines and a minimum follow-up of 3 years. A retrospective central review of planar V/Q scintigraphy was performed by three nuclear physicians blinded to clinical findings and to final diagnosis. The number, extent (sub-segmental or segmental) and type (matched or mismatched) of perfusion defects were reported. Sensitivity and specificity were evaluated for various criteria based on the number of mismatched perfusion defects and the number of perfusion defects (regardless of ventilation). Receiver operating characteristic (ROC) curves were generated and areas under the curve (AUC) were calculated for both. Results: A total of 226 patients with newly diagnosed PH were analyzed. Fifty six (24.8%) were diagnosed with CTEPH while 170 patients (75.2%) were diagnosed with non-CTEPH. The optimal threshold was 2.5 segmental mismatched perfusion defects, providing a sensitivity of 100 % (95% CI 93.6-100%) and a specificity of 94.7% (95%CI 90.3-97.2%). Lower diagnostic cut-offs of mismatched perfusion defects provided similar sensitivity but lower specificity. Ninety five percent of patients with CTEPH had more than 4 segmental mismatched defects. An interpretation only based on perfusion provided similar sensitivity but a specificity of 81.8% (95%CI 75.3-86.9%). Conclusion: Our study confirmed the high diagnostic performance of planar V/Q scintigraphy for the screening of CTEPH in patients with PH. The optimal diagnostic cut-off for interpretation was 2.5 segmental mismatched perfusion defects. An interpretation only based on perfusion defects provided similar sensitivity but lower specificity.

Systemic Artery to Pulmonary Artery Shunt Mimicking Acute Pulmonary Embolism, Unmasked by a Multimodality Imaging Approach.

In this report, we describe the functional imaging findings of systemic artery to pulmonary artery shunt in V/Q SPECT CT imaging. A 63-year-old man with small-cell lung cancer underwent CT pulmonary angiography (CTPA) for suspected acute pulmonary embolism (PE). The CTPA showed an isolated segmental filling defect in the right lower lobe, which was initially interpreted as positive for PE but was actually the consequence of a systemic artery to pulmonary artery shunt due to the recruitment of the bronchial arterial network by the adjacent tumor. A V/Q SPECT/CT scan was also performed, demonstrating a matched perfusion/ventilation defect in the right lower lobe.

Radiation Therapy Planning of Thoracic Tumors: A Review of Challenges Associated With Lung Toxicities and Potential Perspectives of Gallium-68 Lung PET/CT Imaging.

Despite the introduction of new radiotherapy techniques, such as intensity modulated radiation therapy or stereotactic body radiation therapy, radiation induced lung injury remains a significant treatment related adverse event of thoracic radiation therapy. Functional lung avoidance radiation therapy is an emerging concept in the treatment of lung disease to better preserve lung function and to reduce pulmonary toxicity. While conventional ventilation/perfusion (V/Q) lung scintigraphy is limited by a relatively low spatial and temporal resolution, the recent advent of 68Gallium V/Q lung PET/CT imaging offers a potential to increase the accuracy of lung functional mapping and to better tailor lung radiation therapy plans to the individual's lung function. Lung PET/CT imaging may also improve our understanding of radiation induced lung injury compared to the current anatomical based dose-volume constraints. In this review, recent advances in radiation therapy for the management of primary and secondary lung tumors and in V/Q PET/CT imaging for the assessment of functional lung volumes are reviewed. The new opportunities and challenges arising from the integration of V/Q PET/CT imaging in radiation therapy planning are also discussed.

Automatic delineation and quantification of pulmonary vascular obstruction index in patients with pulmonary embolism using Perfusion SPECT-CT: a simulation study.

BACKGROUND: In patients with pulmonary embolism (PE), there is a growing interest in quantifying the pulmonary vascular obtruction index (PVOI), which may be an independent risk factor for PE recurrence. Perfusion SPECT/CT is a very attractive tool to provide an accurate quantification of the PVOI. However, there is currently no reliable method to automatically delineate and quantify it. The aim of this phantom study was to assess and compare 3 segmentation methods for PVOI quantification with perfusion SPECT/CT imaging. METHODS: Three hundred ninety-six SPECT/CT scans, with various PE scenarios (n = 44), anterior to posterior perfusion gradients (n = 3), and lung volumes (n = 3) were simulated using Simind software. Three segmentation methods were assesssed: (1) using an intensity threshold expressed as a percentage of the maximal voxel value (MaxTh), (2) using a Z-score threshold (ZTh) after building a Z-score parametric lung map, and (3) using a relative difference threshold (RelDiffTh) after building a relative difference parametric map. Ninety randomly selected simulations were used to define the optimal threshold, and 306 simulations were used for the complete analysis. Spacial correlation between PE volumes from the phantom data and the delineated PE volumes was assessed by computing DICEPE indices. Bland-Altman statistics were used to calculate agreement for PVOI between the phantom data and the segmentation methods. RESULTS: Mean DICEPE index was higher with the RelDiffTh method (0.85 ± 0.08), as compared with the MaxTh method (0.78 ± 0.16) and the ZTh method (0.67 ± 0.15). Using the RelDiffTh method, mean DICEPE index remained high (> 0.81) regardless of the perfusion gradient and the lung volumes. Using the RelDiffTh method, mean relative difference in PVOI was - 12%, and the limits of agreement were - 40% to 16%. Values were 3% (- 75% to 81%) for MaxTh method and 0% (- 120% to 120%) for ZTh method. Graphycal analysis of the Bland-Altman graph for the RelDiffTh method showed very close estimation of the PVOI for small and medium PE, and a trend toward an underestimation of large PE. CONCLUSION: In this phantom study, a delineation method based on a relative difference parametric map provided a good estimation of the PVOI, regardless of the extent of PE, the intensity of the anterior to posterior gradient, and the whole lung volumes.

Assessment of Image Quality and Lesion Detectability With Digital PET/CT System.

Purpose: The aim of this study was to assess image quality and lesion detectability acquired with a digital Positron Emission Tomography/Computed Tomography (PET/CT) Siemens Biograph Vision 600 system. Material and Methods: Consecutive patients who underwent a FDG PET/CT during the first week of use of a digital PET/CT (Siemens Biograph Vision 600) at the nuclear medicine department of the university hospital of Brest were analyzed. PET were realized using list mode acquisition. For all patients, 4 datasets were reconstructed. We determined, according to phantom measurements, an equivalent time acquisition/reconstruction parameters pair of the digital PET/CT corresponding to an analog PET/CT image quality ("analog-like") as reference dataset. We compared the reference dataset with 3 others digital PET/CT reconstruction parameters, allowing a decrease of emission duration: 60, 90, and 120 s per bed position. Three nuclear medicine physicians evaluated independently, for each dataset, overall image quality [Maximal Intensity Projection (MIP), noise, sharpness] using a 4-point scale. Physicians assessed also lesion detection capability by reporting new visible lesions on each digital datasets with their confidence level in comparison with analog-like dataset. Results: Ninety-eight patients were analyzed. Image quality of MIP (IQMIP), sharpness (IQSHARPNESS), and noise (IQNOISE) of all digital datasets (60, 90, and 120 s) were better than those evaluated with analog-like reconstruction. Moreover, digital PET/CT system improved IQMIP, IQNOISE, and IQSHARPNESS whatever the BMI. Lesion detection capability and confidence level were higher for 60, 90, 120 s per bed position, respectively, than for analog-like images. Conclusion: Our study demonstrated an improvement of image quality and lesion detectability with a digital PET/CT system.

The Impact of Pulmonary Vascular Obstruction on the Risk of Recurrence of Pulmonary Embolism: A French Prospective Cohort.

BACKGROUND: We aimed to assess whether high pulmonary vascular obstruction index (PVOI) measured at the time of pulmonary embolism (PE) diagnosis is associated with an increased risk of recurrent venous thromboembolism (VTE). STUDY DESIGN AND METHODS: French prospective cohort of patients with a symptomatic episode of PE diagnosed with spiral computerized tomography pulmonary angiography (CTPA) or ventilation-perfusion (V/Q) lung scan and a follow-up of at least 6 months after anticoagulation discontinuation. PVOI was assessed based on the available diagnostic exam (V/Q lung scan or CTPA). All patients had standardized follow-up and independent clinicians adjudicated all deaths and recurrent VTE events. Main outcome was recurrent VTE after stopping anticoagulation. RESULTS: A total of 418 patients with PE were included. During a median follow-up period of 3.6 (1.2-6.0) years, 109 recurrences occurred. In multivariate analysis, PVOI ≥ 40% was an independent risk factor for recurrence (hazard ratio 1.77, 95% confidence interval 1.20-2.62, p < 0.01), whether PE was provoked by a major transient risk factor or not. A threshold at 41% was identified as the best value associated with the risk of recurrence 6 months after stopping anticoagulation (area under curve = 0.64). CONCLUSION: PVOI ≥ 40% at PE diagnosis was an independent risk factor for recurrence VTE. Further prospective validation studies are needed.