Ventilation-perfusion Imaging Research Articles

Evaluating the efficacy of balloon pulmonary angioplasty using quantitative analysis of SPECT pulmonary ventilation/perfusion scintigraphy in patients with chronic thromboembolic pulmonary hypertension.

Single-photon emission computed tomography (SPECT) ventilation perfusion imaging is the main imaging method for the diagnosis of pulmonary embolism, and its application in the diagnosis and efficacy evaluation of chronic thromboembolic pulmonary hypertension (CTEPH) has been paid more and more attention. In recent years, with the development of computer software technology, ventilation/perfusion (V/Q) imaging quantitative analysis technology has become more and more mature. The objective of this study was to investigate the utility of quantitative analysis of pulmonary V/Q scintigraphy in evaluating the efficacy of balloon pulmonary angioplasty (BPA) in patients with CTEPH. In this retrospective analysis, we collected data of patients diagnosed with CTEPH who underwent BPA at the China-Japan Friendship Hospital from April 2018 to September 2020. The sample consisted of 23 males and 28 females, with an average age of 55.1±12.7 years. All patients underwent V/Q scintigraphy within one week before surgery, and we reviewed the pulmonary angiography within 1-3 months following the last BPA procedure. We repeated V/Q scintigraphy within 1 week before or after the pulmonary angiography, at the time of collecting clinical and hemodynamic parameters of these patients. We divided the patients into two groups based on the presence of residual pulmonary hypertension post-surgery and compared the pre- and post-operative quantitative pulmonary perfusion defect percentage scores (PPDs%) using the t-test. In all, 102 V/Q scintigraphy scans were performed in 51 patients. The quantitative PPDs% were positively correlated with the hemodynamic indexes mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and mean right ventricular pressure (RVP) (r=0.605, 0.391, and 0.464, respectively, all P<0.001) and negatively correlated with the 6-minute walking distance (6MWD) (r=-0.254, P=0.010). The average preoperative quantitative PPDs% were (49.0±15.6)% which significantly decreased to (33.5±13.9)% after surgery (t=11.249, P<0.001). The preoperative quantitative PPDs% were (54.7±15.7)% and (44.0±13.8)% in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=2.599, P=0.012). The postoperative quantitative PPDs% were (41.5±12.5)% and (26.3±11.0)%, in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=4.647, P<0.001). In this study, we found that quantitative analysis of SPECT pulmonary V/Q scintigraphy adequately reflected the pulmonary artery pressure and clinical status in patients with CTEPH. Our results demonstrate its definite utility in predicting residual pulmonary hypertension and in evaluating the postoperative efficacy of BPA in patients with CTEPH.

Amplified Thrombo-Inflammatory Biomarkers in Pulmonary Embolism with Augmented Responses in Von-Willebrand Factor, Microparticles and Interleukin-6 in Patients with Cancer

Introduction: The multifactorial and complex pathophysiology of pulmonary embolism (PE) involves dysregulation of hemostatic system including fibrinolytic imbalance, endothelial compromise, and generation of thrombotic mediators, along with cellular defects and hemodynamic derangement. These pathophysiologic processes results in the generation of thrombo-inflammatory biomarkers reflecting the endogenous hemostatic imbalance. Cancer is prevalent in PE patients and is considered as an added risk factor for the adverse outcomes. Thrombo-inflammatory biomarker profiling provide means to risk stratify PE patients. This study aimed to profile several of these biomarkers in normal individuals and PE patients and further demonstrate their additional amplification in patients with cancer as a co-morbidity. Materials & Method: Four hundred male and female patients of 18 years or older age, were included through enrolment in conjunction with an IRB approved project by the pulmonary embolism response team (PERT) registry. Diagnosis of PE was confirmed by computed tomography (CT), angiography or ventilation perfusion imaging. Blood samples were drawn with in 24-72 hours of confirmed diagnosis of acute PE. Normal human plasma (NHP) samples were obtained from 50 healthy individuals including 25 male and 25 female and used for referencing purposes. All of the plasma samples were analyzed for D-Dimer, plasminogen activator inhibitor-1 (PAI-1) antigen, tissue-type plasminogen activator (tPA), activated thrombin-activatable fibrinolysis inhibitor (TAFI-a), von Willebrand factor (vWF), c-Reactive Protein (CRP) and interleukin-6 (IL-6) were measured by commercially available ELISA methods. Microparticles were measured by using a chromogenic functional method. Individual biomarkers were compared to normal plasma and further stratified on cancer status and PE severity. Results are presented as mean±SD and fold increase. For the degree of association, GraphPad Prism Software was used. Results: PE patients exhibited varying levels of upregulation of all of the individual biomarkers compared to normal's, D-Dimer (37.05-fold), PAI-1 antigen (3.95-fold), tPA (4.69-fold), TAFI (1.21-fold), vWF (1.89-fold), CRP (35.34-fold), IL-6 (21.62-fold), and microparticles (3.04-fold) increase in PE patients with reference to NHP. When the PE group stratified into cancer and non-cancer patients, most of the biomarkers except D-Dimer and microparticles showed varying degree of modest elevation in the cancer group (figure 1). vWF, IL6 and microparticles levels were found to be further amplified in PE group with cancer. Of these three biomarkers, only vWF remained amplified when stratified by PE severity in patients with cancer, however this change was only observed in the low-grade PE patients (table 1). The IL-6 levels showed increased trend in the low-grade and sub-massive patient group, however because of the wide scatter, it was not significant. Conclusion: These studies demonstrate that thrombo-inflammatory biomarkers are upregulated in PE patients. Furthermore, PE patients with cancer exhibit amplified responses for vWF, IL-6 and microparticles levels suggesting their role in mediating the pathogenesis involving endothelial, inflammatory and thrombogenic mechanisms. Among the biomarkers studied, vWF is central to thrombo-inflammatory process and is distinct in PE cohort with cancer, despite taking into account the lower PE severity. These studies suggest that selective biomarker profiling of thrombo-inflammatory biomarkers may be valuable in the risk stratification and therapeutic management of PE patients at large. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 10876: Thrombo-Inflammatory Biomarkers in Pulmonary Embolism as Stratified in Cancer and Non-Cancer Patient Groups

Introduction: The multifactorial and complex pathophysiology of pulmonary embolism (PE) involves dysregulation of hemostatic system including fibrinolytic imbalance, endothelial compromise, and generation of thrombotic mediators, along with cellular defects and hemodynamic derangement. Cancer is prevalent in PE patients and is considered an added risk factor for the adverse outcomes. Thrombo-inflammatory biomarkers profiling provide means to risk stratify PE patients. Hypothesis: This study aimed to profile several of these biomarkers in normal and PE patients and to further demonstrate any potential difference between cancer and non-cancer patients. Methods: Four hundred patients of 18 years or older age, were included through enrolment in conjunction with IRB approved project by the pulmonary embolism response team (PERT) registry. Diagnosis of PE was confirmed by computed tomography (CT), angiography or ventilation perfusion imaging. Blood samples were drawn with in 24 hours of confirmed diagnosis of acute PE. Control plasma samples were obtained from 50 healthy individuals. All plasma samples were analyzed for D-Dimer, PAI-1 antigen, tPA, TAFI-a, vWF, CRP, troponin and IL-6 were measured by ELISA methods. Microparticles were measured using a chromogenic functional method. Individual biomarkers were compared to normal plasma and further stratified into cancer and non-cancer. Results: All the individual biomarkers exhibited up to 50-fold elevation in PE patients compared to normal groups. D-Dimer and CRP showed the most pronounced increase. When the PE group stratified into cancer and non-cancer patients, most of the biomarkers except D-Dimer and microparticles showed varying degree of modest elevation in the cancer group. vWF, IL6 and microparticles levels were found to be significantly different in the cancer group (p&lt;0.050). Conclusions: These studies demonstrate that thrombo-inflammatory biomarkers are upregulated in PE patients. Furthermore, PE patients with cancer exhibit amplified levels of some of the markers suggesting the increased severity of pathogenesis involving thrombo-inflammatory mechanisms.

VENTRICULAR-ARTERIAL DECOUPLING IS ASSOCIATED WITH IN-HOSPITAL ADVERSE EVENTS IN NORMOTENSIVE PULMONARY EMNBOLISM

VENTRICULAR-ARTERIAL DECOUPLING IS ASSOCIATED WITH IN-HOSPITAL ADVERSE EVENTS IN NORMOTENSIVE PULMONARY EMNBOLISM

Age adjusted D-dimer cutoffs for pulmonary embolism in a geriatric population utilizing a D-dimer unit assay.

Age adjusted serum d-dimer (AADD) with clinical decision rules have been utilized to rule out pulmonary embolism (PE) in low-risk patients; however, its use in the geriatric population has been questioned and the use of d-dimer unit (DDU) assay is uncommon. The present study aims to compare the test characteristics of the AADD (age × 5) measured in DDU with the standard cutoff (DDU<250) and study hospital laboratory's d-dimer cutoff (DDU<600) in geriatric patients presenting with suspected PE. This retrospective study enrolled patients ≥65years old with suspected PE and d-dimer performed between January 1, 2019 and December 31, 2019 who presented to the emergency department (ED). Charts were reviewed for CTA chest and ventilation perfusion imaging results for PE. Diagnostic parameters for each cutoff were calculated for the primary outcome. 510 patients were included, 20 with PE. There was no significant difference between the sensitivities of AADD (100%, 95% CI: 80-100), standard cutoff (100%, 95% CI: 80-100), and hospital cutoff (90%, 95% CI: 66.9-98.2). The hospital cutoff specificity (22.7%, 95% CI: 17.1-29.3) was significantly greater than the AADD (13.4%, 95% CI: 9.1-19.2) and standard cutoff (10.8%, 95% CI: 7.0-16.3) specificities. In geriatric patients presenting to the ED with suspected PE, the AADD measured in DDUs maintained sensitivity with improved specificity compared to standard cutoff. In this population, the AADD would have safely reduced imaging by 19% without missing any PEs. AADD remains a valid tool with high sensitivity and negative predictive value in ruling out PE in geriatric patients.

Fibrinolytic Dysregulation Contributes to the Hypercoagulable State in Pulmonary Embolism Patients

Introduction: The multifactorial and complex pathophysiology of pulmonary embolism (PE) involves dysregulation of hemostatic system including fibrinolytic imbalance, endothelial compromise and generation of thrombotic mediators, along with cellular defects and hemodynamic derangement. It is estimated that 6000 cases of pulmonary embolism and DVT are reported yearly of which 1000 result in death. PE evolves from a pre-existing venous thrombus, obstructing pulmonary artery leading to pulmonary failure. The progression of clot formation results in increase in right ventricular pressure, systemic hypoperfusion, hypoxemia ischemia and eventually multi organ failure. Fibrinolytic dysregulation and generation of procoagulant mediators result in increased clot burden and lead to adverse outcomes. Profiling of the component of the fibrinolytic system for such mediators as the activators and inhibitors of fibrinolysis, vWF and cellular microparticles may provide additional insights into the pathogenesis of PE. The purpose of this study is to profile plasma samples from PE patients for various mediators of hemostatic dysregulation which contribute to the fibrinolytic dysregulation in PE patients.Material & Method: Seventy-eight patients of 18 years or older age, were included in this study through enrolment conducted in conjunction with an ongoing IRB approved project by the pulmonary embolism response team (PERT) registry. Diagnosis of PE was confirmed by computed tomography (CT), angiography or ventilation perfusion imaging. Blood samples were drawn with in 24 hours of confirmed diagnosis of acute PE in 3.2% sodium citrate tubes at the time of diagnosis, processed for platelet poor plasma and frozen. Control plasma samples were obtained from 50 healthy individuals. Both the patient and control plasma samples were analyzed for D-Dimer, PAI-1 antigen, tPA, TAFI-a, protein C, alpha-2 antiplasmin, microparticles and vWF using ELISA methods (Hypen Biomedical, Franklin, Ohio). A functional PAI-1 chromogenic substrate method and an ELISA based uPA antigen method was used (Biomedica, Halifax, Nova Scotia, Canada). Circulating levels of each of the individual biomarkers were compared to normal plasma, descriptive statistics including non-parametric Mann-Whitney t-test and spearman correlation coefficient analysis was carried out by using GraphPad Prism software. Percent Increase from the normal mean was calculated for each individual parameter. p value <0.05 was considered statistically significant.Result: In comparison to normal group, the PE patients exhibited varying levels of increase in the D-Dimer, tPA, uPA, PAI-1 antigen, PAI-1 functional, TAFI antigen, microparticles and vWF, whereas decreased levels were noted for protein C and alpha-2 antiplasmin as shown on Figure 1. D-Dimer showed the most pronounced increase (368.2-fold) followed by tPA (165.9-fold), PAI-1 antigen (3.91-fold), microparticles (2.14-fold), vWF (1.83-fold), uPA (0.5-fold), TAFI antigen (0.40-fold) and PAI-1 functional (0.34-fold). In correlation analysis, D-Dimer negatively correlated with TAFI antigen (r= -0.3106) and alpha-2 antiplasmin (r= -0.3056), functional PAI-1 levels positively correlated with tPA (r= 0.3117) and protein C (r= 0.4059), tPA negatively correlated with TAFI antigen (r= -0.4601), alpha-2 antiplasmin (r= -0.2460) and positively correlated with microparticles (r= 0.2456) , TAFI antigen positively correlated with protein C (r= 0.3612), alpha-2 antiplasmin (r= 0.3899) and negatively correlated with microparticles (r= -0.2470) whereas protein C showed a negative correlation with vWF (r= -0.2838).Conclusion: The markedly increased D-Dimer levels suggest increase clot burden in PE patients. tPA antigen is also markedly increased, whereas the uPA showed modest increase which may suggest compensatory upregulation, PAI-1 antigen levels were much higher in comparison to PAI-1 functional activity, suggesting consumption of this inhibitor. Decreased alpha-2 antiplasmin and protein C levels also suggest consumption. Increased TAFI antigen contribute to the clot resistant to fibrinolysis. Cellular consumption and endothelial dysfunction results in increased in vWF and microparticles promoting thrombogenesis. Measurement of these biomarkers may be useful in the understanding of the pathogenesis, risk stratification and clinical management of PE patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Is Perfusion Dose-Response Different Than Ventilation Dose-Response for Lung Cancer Patients Treated With Radiotherapy?

Ventilation-perfusion dose-response studies have focused on using functional imaging to characterize a dose-response and to assess whether the dose-response can predict subsequent pulmonary toxicity. Current dose-response studies typically focus on a single modality (ventilation or perfusion) and perform assessments on a population-based basis. There is no work evaluating whether ventilation dose-response differs from perfusion dose-response for individual lung cancer patients. The purpose of this study was to use single photon emission computed tomography (SPECT)-CT ventilation-perfusion imaging to quantitatively and clinically evaluate whether lung cancer patients treated with radiotherapy have differences between their ventilation and perfusion dose-responses.Twenty patients with biopsy proven lung cancer enrolled on a prospective functional avoidance protocol underwent SPECT-CT perfusion-ventilation scans pre- and 3-month post-radiotherapy. The SPECT-CT, planning CT, and dose distribution were rigidly registered. We calculated the relative changes in pre- to post-treatment ventilation-perfusion in lung regions receiving ≥ 20 Gy (referred to as ΔPV20 for perfusion and ΔVV20 for ventilation). Differences between perfusion-based ΔPV20 and ventilation-based ΔVV20 were assessed and referred to as ΔfV20. A radiologist read each pre- and post-treatment ventilation-perfusion scans using a semi-quantitative scale that assigned a score ranging from 1 to 8 that reflected functional defect and heterogeneity in each lung. The difference between radiologist scores for the pre- and post-treatment scans was calculated for both ventilation and perfusion. Differences between ventilation-based and perfusion-based radiologist scores were assessed.Twenty-five percent of patients had a difference of ΔfV20 > 35% between ventilation-perfusion pre- to post-treatment changes (ΔVV20 and ΔPV20) and 20% of patients had opposite directions for ventilation-perfusion pre- to post-treatment changes. Radiologist assessment resulted in 20% of patients having different ventilation-perfusion semi-quantitative change scores for ipsilateral lungs.The current work employed quantitative metrics and clinical assessments to evaluate whether ventilation dose-response differs from perfusion dose-response for individual lung cancer patients. Our data showed that ventilation dose-response can differ from perfusion dose-response for 20% to 30% of patients. Our study demonstrates that when evaluating functional dose-response for lung cancer patients, it is insufficient to look at ventilation or perfusion alone for a subset of patients; but rather both modes of functional imaging may be needed when predicting for clinical outcomes.

Unilateral absence of pulmonary artery: A rare cause of dyspnea in a 77-year-old woman

Isolated unilateral absence of pulmonary artery is quite rare and usually associated with congenital cardiac defects. It is usually diagnosed in childhood with recurrent respiratory tract infections and signs of pulmonary hypertension. It rarely remains asymptomatic until adulthood and may present with dyspnea, hemoptysis, and recurrent respiratory infections later, while it can rarely be an incidental finding of other imaging. Surgical management in early days of life will prevent pulmonary hypertension while in adults it is aimed to treat the complications. Here, we report the case of a 77-year-old female, a mother of five children. She came with worsening of dyspnea for a week, and her computed tomography pulmonary angiography showed absence of left pulmonary artery accompanying hypoplastic lung. Ventilation perfusion imaging showed absence of perfusion of the left lung. She had severe pulmonary hypertension and was managed with long-term oxygen therapy, diuretics, and vasodilators.

Physician Receptiveness of Ventilation-Perfusion Imaging in a Randomized Clinical Trial

Background and Hypothesis: Computed Tomography of the pulmonary arteries (CTPA) is the most common imaging modality for evaluating patients for suspected pulmonary embolism (PE), but carries the risk of acute kidney injury (AKI) from contrast media exposure. In appropriately selected patients, ventilation scintigraphy (VQ) imaging is a diagnostically equivalent alternative. We hypothesized that physician perceptions of diagnostic accuracy and study availability contribute to under-utilization of VQ imaging.&#x0D; Project Methods: Patients with suspected PE at increased risk of acute kidney injury, were randomly selected to undergo VQ instead of CTPA. Patients unable to consent, patients with a history of pulmonary surgery, and those undergoing contrastenhanced imaging for other indications were excluded. A screening chest radiograph was obtained prior to study imaging allocation. All cases were reviewed by a nuclear medicine radiologist blinded to acceptance or refusal of VQ imaging allocation. The primary outcome was defined as the rate of physician-refusal of VQ imaging. The unprompted physician-reported reason for refusal was recorded, in real-time, along with any other general responses.&#x0D; Results: Following exclusions, 42 subjects were enrolled. Notably, chest radiograph findings excluded only 2 subjects. The reviewing nuclear radiologist agreed with all study-selections for VQ appropriateness and there was no instance of nondiagnostic VQ imaging. Treating physicians refused VQ imaging randomization in 48% (20/42). Physicians also believed VQ imaging lacked sufficient diagnostic accuracy in the context of active non-pulmonary malignancy in 29% (12/42) of cases. Although CT did not identify cases not seen on chest radiograph, in 12% (5/42) cases suspected pneumonia was the reason for refusal. Statements such as “VQ is inferior [for PE],” and “VQ takes too long” were characteristic of general responses from treating providers.&#x0D; Conclusion and Potential Impact: VQ imaging remains under-utilized in patients at risk of AKI. Perceived limitations to diagnostic accuracy and study availability are contributors to under-utilization.

A case series of outcomes in isolated subsegmental pulmonary embolism on ventilation-perfusion imaging.

The risk of recurrent venous thromboembolic disease and the management of patients with isolated subsegmental pulmonary embolism (SSPE) remain unclear. We sought to assess the long-term clinical outcome of patients with isolated SSPE demonstrated by isolated subsegmental mismatch found on ventilation/perfusion (V/Q) scans. We performed a retrospective observational study of 1300 consecutive patients with suspected pulmonary embolism who underwent index V/Q single-photon emission computed tomography between 2012 and 2013. Forty (3%) patients were found to have isolated SSPE identified on V/Q scan. Of the 40 patients with isolated SSPE on V/Q scan, 19 underwent further investigation with computed tomography pulmonary angiogram (CTPA) within 48 h. Among 19 patients who had corroborating CTPA performed concurrently, 94.7% of the SSPEs identified on V/Q were not detectable on CTPA. Of the 40 patients, 10 (25%) were anticoagulated. In a median follow-up of 3.28±0.55 years, all-cause mortality occurred in two patients, recurrence of suspected venous thromboembolism (VTE) occurred in 12 (30%) of 40 patients, but none had confirmed recurrent thromboembolism on further imaging. In the 40 patients with SSPE on V/Q, there was no difference in the risk of recurrence of suspected VTE or mortality between patients treated with anticoagulation and not treated (hazard ratio: 2.04, 95% confidence interval: 0.75-7.28). In this case series, a large proportion of patients with isolated SSPE on V/Q imaging were not identified on corroborating CTPA performed within 48 h. In patients with isolated SSPE (identified by isolated subsegmental mismatch on V/Q single-photon emission computed tomography), we found no difference in risk of recurrent suspected VTE or all-cause mortality in those treated with anticoagulation and those not treated.

The Importance of Quality in Ventilation-Perfusion Imaging.

As the health care environment continues to change and morph into a system focusing on increased quality and evidence-based outcomes, nuclear medicine technologists must be reminded that they play a critical role in achieving high-quality, interpretable images used to drive patient care, treatment, and best possible outcomes. A survey performed by the Quality Committee of the Society of Nuclear Medicine and Molecular Imaging Technologist Section demonstrated that a clear knowledge gap exists among technologists regarding their understanding of quality, how it is measured, and how it should be achieved by all practicing technologists regardless of role and education level. Understanding of these areas within health care, in conjunction with the growing emphasis on evidence-based outcomes, quality measures, and patient satisfaction, will ultimately elevate the role of nuclear medicine technologists today and into the future. The nuclear medicine role now requires technologists to demonstrate patient assessment skills, practice safety procedures with regard to staff and patients, provide patient education and instruction, and provide physicians with information to assist with the interpretation and outcome of the study. In addition, the technologist must be able to evaluate images by performing technical analysis, knowing the demonstrated anatomy and pathophysiology, and assessing overall quality. Technologists must also be able to triage and understand the disease processes being evaluated and how nuclear medicine diagnostic studies may drive care and treatment. Therefore, it is imperative that nuclear medicine technologists understand their role in the achievement of a high-quality, interpretable study by applying quality principles and understanding and using imaging techniques beyond just basic protocols for every type of disease or system being imaged. This article focuses on quality considerations related to ventilation-perfusion imaging. It provides insight on appropriate imaging techniques and protocols, true imaging variants and tracer distributions versus artifacts that may result in a lower-quality or misinterpreted study, and the use of SPECT and SPECT/CT as an alternative providing a high-quality, interpretable study with better diagnostic accuracy and fewer nondiagnostic procedures than historical planar imaging.

Bronchopulmonary sequestration as a cause of mismatched perfusion defect on single-photon emission computed tomography ventilation-perfusion scan

We present a 46-year-old female with pleuritic chest pain on a background of pulmonary embolism diagnosed on a single-photon emission computed tomography (SPECT) ventilation-perfusion (V/Q) imaging 3 years earlier. A SPECT V/Q scan detected a mismatched perfusion defect in the posterior basal segment of the right lower lobe, essentially unchanged from a defect identified 3 years earlier. Given the atypical finding, the patient went on to have a computed tomographic pulmonary angiogram. It revealed an intralobar bronchopulmonary sequestration as the cause of the right lower lobe mismatched perfusion defect. With growing awareness of radiation safety, the number of V/Q imaging studies being undertaken to investigate suspected pulmonary emboli, especially in young female patients, has increased. This case report serves as a timely reminder of the potential pitfalls associated with V/Q scan image interpretation.

New developments and future challenges of nuclear medicine and molecular imaging for pulmonary embolism

Although widely validated, current tests for pulmonary embolism (PE) diagnosis, i.e. computed tomography pulmonary angiography (CTPA) and V/Q planar scintigraphy, have some limitations. Drawbacks of CTPA include the radiation dose, some contra indications and a rising concern about a possible overdiagnosis/overtreatment of PE. On the other hand, V/Q planar scintigraphy has a high rate of non-diagnostic tests responsible for complex diagnostic algorithms.Since the PIOPED study, imaging equipment and radiopharmaceuticals have greatly evolved allowing the introduction of techniques that improve imaging of lung ventilation and perfusion. Single photon emission computed tomography (SPECT) and SPECT/CT techniques are already largely used in daily practice and have been described to have greater diagnostic performance and much fewer non-diagnostic tests as compared with planar scintigraphy. However, they have not yet been firmly validated in large scale prospective outcome studies. More recently, it has also been proposed to image pulmonary perfusion and ventilation using positron emission tomography (PET), which has an inherent technical superiority as compared to conventional scintigraphy and may provide new insight for pulmonary embolism. Regardless of modality, these new thoracic imaging modalities have to be integrated into diagnostic strategies.The other major challenge for venous thromboembolism diagnosis may be the potential additional value of molecular imaging allowing specific targeting of thrombi in order, for example, to differentiate venous thromboembolism from tumor or septic thrombus, or acute from residual disease.In this article, the new imaging procedures of lung ventilation perfusion imaging with SPECT, SPECT/CT and PET/CT are discussed. We also review the current status and future challenge of molecular imaging for the in vivo characterization of venous thromboembolism.

Overview of the Novel and Improved Pulmonary Ventilation-Perfusion Imaging Applications in the Era of SPECT/CT.

In this article, we describe the concepts of ventilation-perfusion planar, SPECT, and SPECT/CT and outline the advantages of integrated ventilation-perfusion SPECT/CT over planar imaging. We present an overview of the traditional and new applications of ventilation-perfusion scintigraphy. SPECT/CT has improved the diagnostic accuracy of ventilation-perfusion imaging and opened the door for a new spectrum of applications.

Historical Evolution of Imaging Techniques for the Evaluation of Pulmonary Embolism.

As we celebrate the 100th anniversary of the founding of the Radiological Society of North America (RSNA), it seems fitting to look back at the major accomplishments of the radiology community in the diagnosis of pulmonary embolism. Few diseases have so consistently captured the attention of the medical community. Since the first description of pulmonary embolism by Virchow in the 1850s, clinicians have struggled to reach a timely diagnosis of this common condition because of its nonspecific and often confusing clinical picture. As imaging tests started to gain importance in the 1900s, the approach to diagnosing pulmonary embolism also began to change. Rapid improvements in angiography, ventilation-perfusion imaging, and cross-sectional imaging modalities such as computed tomography (CT) and magnetic resonance imaging have constantly forced health care professionals to rethink how they diagnose pulmonary embolism. Needless to say, the way pulmonary embolism is diagnosed today is distinctly different from how it was diagnosed in Virchow's era; and imaging, particularly CT, now forms the cornerstone of diagnostic evaluation. Currently, radiology offers a variety of tests that are fast and accurate and can provide anatomic and functional information, thus allowing early diagnosis and triage of cases. This review provides a historical journey into the evolution of these imaging tests and highlights some of the major breakthroughs achieved by the radiology community and RSNA in this process. Also highlighted are areas of ongoing research and development in this field of imaging as radiologists seek to combat some of the newer challenges faced by modern medicine, such as rising health care costs and radiation dose hazards.

Accuracy and Utility of Deformable Image Registration in 68Ga 4D PET/CT Assessment of Pulmonary Perfusion Changes During and After Lung Radiation Therapy

Measuring changes in lung perfusion resulting from radiation therapy dose requires registration of the functional imaging to the radiation therapy treatment planning scan. This study investigates registration accuracy and utility for positron emission tomography (PET)/computed tomography (CT) perfusion imaging in radiation therapy for non-small cell lung cancer. (68)Ga 4-dimensional PET/CT ventilation-perfusion imaging was performed before, during, and after radiation therapy for 5 patients. Rigid registration and deformable image registration (DIR) using B-splines and Demons algorithms was performed with the CT data to obtain a deformation map between the functional images and planning CT. Contour propagation accuracy and correspondence of anatomic features were used to assess registration accuracy. Wilcoxon signed-rank test was used to determine statistical significance. Changes in lung perfusion resulting from radiation therapy dose were calculated for each registration method for each patient and averaged over all patients. With B-splines/Demons DIR, median distance to agreement between lung contours reduced modestly by 0.9/1.1 mm, 1.3/1.6 mm, and 1.3/1.6 mm for pretreatment, midtreatment, and posttreatment (P < .01 for all), and median Dice score between lung contours improved by 0.04/0.04, 0.05/0.05, and 0.05/0.05 for pretreatment, midtreatment, and posttreatment (P < .001 for all). Distance between anatomic features reduced with DIR by median 2.5 mm and 2.8 for pretreatment and midtreatment time points, respectively (P = .001) and 1.4 mm for posttreatment (P > .2). Poorer posttreatment results were likely caused by posttreatment pneumonitis and tumor regression. Up to 80% standardized uptake value loss in perfusion scans was observed. There was limited change in the loss in lung perfusion between registration methods; however, Demons resulted in larger interpatient variation compared with rigid and B-splines registration. DIR accuracy in the data sets studied was variable depending on anatomic changes resulting from radiation therapy; caution must be exercised when using DIR in regions of low contrast or radiation pneumonitis. Lung perfusion reduces with increasing radiation therapy dose; however, DIR did not translate into significant changes in dose-response assessment.

Non-invasive quantitative pulmonary V/Q imaging using Fourier decomposition MRI at 1.5T

ObjectivesTechniques for quantitative pulmonary perfusion and ventilation using the Fourier Decomposition method were recently demonstrated. We combine these two techniques and show that ventilation-perfusion (V/Q) imaging is possible using only a single MR acquisition of less than thirty seconds. MethodsThe Fourier Decomposition method is used in combination with two quantification techniques, which extract baselines from within the images themselves and thus allows quantification. For the perfusion, a region assumed to consist of 100% blood is utilized, while for the ventilation the zero-frequency component is used. V/Q-imaging is then done by dividing the quantified ventilation map with the quantified perfusion map. The techniques were used on ten healthy volunteers and fifteen patients diagnosed with lung cancer. ResultsA mean V/Q-ratio of 1.15±0.22 was found for the healthy volunteers and a mean V/Q-ratio of 1.93±0.83 for the non-afflicted lung in the patients. Mean V/Q-ratio in the afflicted (tumor-bearing) lung was found to be 1.61±1.06. Functional defects were clearly visible in many of the patient images, but 5 of 15 patient images had to be excluded due to artifacts or low SNR, indicating a lack of robustness. ConclusionNon-invasive, quantitative V/Q-imaging is possible using Fourier Decomposition MRI. The method requires only a single acquisition of less than 30seconds, but robustness in patients remains an issue.

Comparison of 4-Dimensional Computed Tomography Ventilation With Nuclear Medicine Ventilation-Perfusion Imaging: A Clinical Validation Study

Four-dimensional computed tomography (4DCT) ventilation imaging provides lung function information for lung cancer patients undergoing radiation therapy. Before 4DCT-ventilation can be implemented clinically it needs to be validated against an established imaging modality. The purpose of this work was to compare 4DCT-ventilation to nuclear medicine ventilation, using clinically relevant global metrics and radiologist observations. Fifteen lung cancer patients with 16 sets of 4DCT and nuclear medicine ventilation-perfusion (VQ) images were used for the study. The VQ-ventilation images were acquired in planar mode using Tc-99m-labeled diethylenetriamine-pentaacetic acid aerosol inhalation. 4DCT data, spatial registration, and a density-change-based model were used to compute a 4DCT-based ventilation map for each patient. The percent ventilation was calculated in each lung and each lung third for both the 4DCT and VQ-ventilation scans. A nuclear medicine radiologist assessed the VQ and 4DCT scans for the presence of ventilation defects. The VQ and 4DCT-based images were compared using regional percent ventilation and radiologist clinical observations. Individual patient examples demonstrate good qualitative agreement between the 4DCT and VQ-ventilation scans. The correlation coefficients were 0.68 and 0.45, using the percent ventilation in each individual lung and lung third, respectively. Using radiologist-noted presence of ventilation defects and receiver operating characteristic analysis, the sensitivity, specificity, and accuracy of the 4DCT-ventilation were 90%, 64%, and 81%, respectively. The current work compared 4DCT with VQ-based ventilation using clinically relevant global metrics and radiologist observations. We found good agreement between the radiologist's assessment of the 4DCT and VQ-ventilation images as well as the percent ventilation in each lung. The agreement lessened when the data were analyzed on a regional level. Our study presents an important step for the integration of 4DCT-ventilation into thoracic clinical practice.

Assessing the utility of the ventilation phase in ventilation–perfusion imaging for acute pulmonary embolism

This study aims to identify patient characteristics that allow the exclusion of the ventilation phase in ventilation-perfusion imaging for the evaluation of acute pulmonary embolism (PE). A total of 500 consecutive ventilation-perfusion reports with an indication for possible acute PE were retrospectively reviewed. Information on ventilation abnormalities, perfusion defects, PIOPED classification, age, sex, chest radiograph results, and presence of respiratory disease was recorded. Patients with moderate and large perfusion defects were analyzed to assess the utility of the ventilation phase on the final PIOPED classification. Moderate (n=39) or large (n=26) perfusion defects were seen in 65 (13%) studies. Of these, 46 studies (70.8%) had defects unmatched on ventilation and three (4.6%) had triple-match defects, resulting in 49 reports (75.4%) classified as intermediate (n=28) or high (n=21) probability for PE. There was a statistically significant association between unmatched defects and a clear chest radiograph (P=0.03) and an association approaching statistical significance with younger age (P=0.05). There was a strong association with respiratory disease (P=0.12) and no association with patient sex (P=0.82). The percentage of studies with unmatched defects increased from 70.8 to 76.7% (33/43, P=0.39) if patients with respiratory disease were excluded, to 82.4% (28/34, P=0.14) if abnormal chest radiographs were excluded, and to 95.7% (22/23, P=0.01) if both were excluded. There may be a subset of patients - younger patients with clear chest radiographs and no respiratory disease - for whom the ventilation phase can be excluded and the determination of a PE is based solely on perfusion abnormalities.

68Ga PET/CT Ventilation–Perfusion Imaging for Pulmonary Embolism: A Pilot Study with Comparison to Conventional Scintigraphy

Ventilation-perfusion (V/Q) scintigraphy is established for regional assessment of lung function in a variety of diseases, including pulmonary embolism (PE). PET/CT may further improve the accuracy and utility of V/Q imaging because of its superior technical characteristics. This pilot study assessed the feasibility of performing V/Q PET/CT and compared diagnostic utility with conventional V/Q imaging in patients with clinical suspicion of PE. Ten patients undergoing conventional V/Q imaging were prospectively recruited. PET/CT V/Q imaging was performed after inhalation of (68)Ga-carbon nanoparticles ("Galligas") and administration of (68)Ga-macroaggregated albumin. Blinded to the results of the other study, SPECT/CT (n = 9) or SPECT (n = 1) images and PET/CT images were graded by a predefined scoring system for scan quality. The number of matched or unmatched defects and diagnosis were also measured and compared with a final diagnosis. PET image quality was equivalent or superior to SPECT in all patients, with more homogeneous radiotracer distribution for both ventilation and perfusion studies (P < 0.01). Based on conventional V/Q imaging, the diagnosis was acute PE in 2 patients and no PE in 7 patients, and the imaging results were nondiagnostic in 1 patient. The PET/CT diagnosis was concordant in 8 patients, and these studies demonstrated a similar number and distribution of matched and unmatched defects. In 1 discordant case, a patient with a SPECT/CT study that was nondiagnostic because of severe airway disease showed no PE on PET/CT. In another, the diagnosis of PE established on SPECT/CT was not reported on PET/CT 2 d later, possibly because of interval clot lysis or migration. This intraindividual comparative study demonstrated that V/Q PET/CT with (68)Ga-labeled radiotracers can be performed in clinical practice. Compared with conventional V/Q imaging, advantages include higher-resolution, fully tomographic images with potentially better regional quantitation of lung function. The short half-life of (68)Ga also enables more flexible acquisition protocols with the option of performing ventilation studies selectively on patients with abnormal perfusion. On the basis of our results, further studies are indicated to assess whether V/Q PET/CT can improve diagnostic algorithms for patients with suspected PE.