Extensive Nonsegmental Pulmonary Perfusion Defects on SPECT/CT as an Early Sign of COVID-19 Infection.

We describe a hospitalized patient with confirmed coronavirus disease 2019 in whom the initial chest computed tomography (CT) was negative, while subsequent perfusion single-photon emission computed tomography/computed tomography imaging revealed extensive nonsegmental perfusion defects in addition to newly developing parenchymal densities. Possible reasons for these findings and their relationship to the multisystem severe acute respiratory syndrome coronavirus 2 infection are discussed in this article.

Assessment of Ventilation and Perfusion in Patients with COVID-19 Discloses Unique Information of Pulmonary Function to a Clinician: Case Reports of V/P SPECT.

V/P SPECT from 4 consecutive patients with COVID-19 suggests that ventilation and perfusion images may be applied to diagnose or exclude pulmonary embolism, verify nonsegmental diversion of perfusion from the ventilated areas (dead space ventilation) that may represent inflammation of the pulmonary vasculature, detect the reversed mismatch of poor ventilation and better preserved perfusion (shunt perfusion) in bilateral pulmonary inflammation and indicate redistribution of lung perfusion (antigravitational hyperperfusion) due to cardiac congestion. V/P mismatch and reversed mismatch may be extensive enough to diminish dramatically preserved matching ventilation/perfusion and to induce severe hypoxemia in COVID-19.

Imaging for precision medicine: can V-P SPECT measure mepolizumab response in asthma?

Monoclonal antibody therapies are effective for many but not all people with severe asthma. Precision medicine guides treatment selection using biomarkers to select patients most likely to respond according to their inflammatory endotypes. However, when assessing response to treatment, greater precision is required. We report a case series describing treatment response to mepolizumab in four severe asthma patients, assessed by traditional methods and with objective ventilation/perfusion single photon emission computed tomography (V-P SPECT). In this series, patients with severe asthma received mepolizumab treatment with clinical outcomes recorded at commencement and at approximately 16 weeks post-treatment initiation. V-P SPECT imaging was performed before and after treatment to determine ventilation heterogeneity and perfusion, and its ability to assess treatment responsiveness. V-P SPECT shows promise as an objective measure to assess lung ventilation and perfusion to observe and assess responsiveness to mepolizumab. With quantification, this measure may allow better precision in determining treatment improvements.

EANM guideline for ventilation/perfusion single-photon emission computed tomography (SPECT) for diagnosis of pulmonary embolism and beyond.

These guidelines update the previous EANM 2009 guidelines on the diagnosis of pulmonary embolism (PE). Relevant new aspects are related to (a) quantification of PE and other ventilation/perfusion defects; (b) follow-up of patients with PE; (c) chronic PE; and (d) description of additional pulmonary physiological changes leading to diagnoses of left ventricular heart failure (HF), chronic obstructive pulmonary disease (COPD) and pneumonia. The diagnosis of PE should be reported when a mismatch of one segment or two subsegments is found. For ventilation, Technegas or krypton gas is preferred over diethylene triamine pentaacetic acid (DTPA) in patients with COPD. Tomographic imaging with V/PSPECT has higher sensitivity and specificity for PE compared with planar imaging. Absence of contraindications makes V/PSPECT an essential method for the diagnosis of PE. When V/PSPECT is combined with a low-dose CT, the specificity of the test can be further improved, especially in patients with other lung diseases. Pitfalls in V/PSPECT interpretation are discussed. In conclusion, V/PSPECT is strongly recommended as it accurately establishes the diagnosis of PE even in the presence of diseases like COPD, HF and pneumonia and has no contraindications.

Ventilation/Perfusion SPECT Imaging-Diagnosing Other Cardiopulmonary Diseases Beyond Pulmonary Embolism.

Ventilation/perfusion single-photon emission computed tomography (V/P SPECT) is the scintigraphic technique recommended primarily for the diagnosis of acute pulmonary embolism (PE) and is golden standard for the diagnosis of chronic PE. Furthermore, interpreting ventilation and corresponding perfusion images enables pattern recognition of many other cardiopulmonary disorders that affect lung function and also allows quantification of their extent. Using Technegas for the ventilation imaging, grading of small airway disease in COPD is possible and the method is recommended for PE diagnosis in patients with severe COPD that is not possible with radiolabelled liquid aerosols. An optimal combination of nuclide activities, acquisition times for ventilation and perfusion, collimators, and imaging matrix yields an adequate V/P SPECT study in approximately 20 minutes of imaging time. The holistic interpretation strategy of V/P SPECT uses all relevant information about the patient and ventilation/perfusion patterns. PE is diagnosed when there is more than one subsegment showing a V/P mismatch representing an anatomic lung unit. Apart from PE, other pathologies should be identified and reported, such as obstructive lung disease, heart failure, and pneumonia according to the European Association of Nuclear Medicine guidelines.

Diagnosing and grading heart failure with tomographic perfusion lung scintigraphy: validation with right heart catheterization.

AIMS: Pulmonary congestion remains a diagnostic challenge in patients with heart failure (HF). The recommended method, chest X-ray (CXR), lacks in accuracy, whereas quantitative tomographic lung scintigraphy [ventilation/perfusion single-photon emission computed tomography (V/P SPECT)] has shown promising results but needs independent validation. The aim of this study is to evaluate V/P SPECT as a non-invasive method to assess and quantify pulmonary congestion in HF patients, using right heart catheterization as reference method. The secondary objective was to investigate the performance of V/P SPECT in the clinical setting compared with CXR. METHODS AND RESULTS: Forty-six consecutive patients with HF that were under consideration for heart transplantation were studied prospectively. All participants were examined with V/P SPECT, CXR, and right heart catheterization. Pulmonary artery wedge pressure served as reference method. Quantitative perfusion gradients were derived from V/P SPECT images. Ventilation/perfusion single-photon emission computed tomography images were also assessed both by expert readers and clinical nuclear medicine physicians. Expert readers correctly identified 87% of all patients with an elevated pulmonary artery wedge pressure > 15 mmHg. The average sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for V/P SPECT assessed by the expert readers were 87%, 72%, 85%, and 75%, respectively. In the clinical nuclear medicine setting, V/P SPECT had 87% sensitivity, 63% specificity, 81% PPV, and 71% NPV. Clinically, V/P SPECT outperformed CXR, which had 27% sensitivity, 75% specificity, 67% PPV, and 35% NPV. CONCLUSIONS: Ventilation/perfusion single-photon emission computed tomography can be used as a non-invasive method to diagnose and quantify pulmonary congestion in patients with HF and is more accurate than CXR in diagnosing pulmonary congestion in the clinical setting.

Automatic lung segmentation in functional SPECT images using active shape models trained on reference lung shapes from CT.

OBJECTIVE: Image segmentation is an essential step in quantifying the extent of reduced or absent lung function. The aim of this study is to develop and validate a new tool for automatic segmentation of lungs in ventilation and perfusion SPECT images and compare automatic and manual SPECT lung segmentations with reference computed tomography (CT) volumes. METHODS: A total of 77 subjects (69 patients with obstructive lung disease, and 8 subjects without apparent perfusion of ventilation loss) performed low-dose CT followed by ventilation/perfusion (V/P) SPECT examination in a hybrid gamma camera system. In the training phase, lung shapes from the 57 anatomical low-dose CT images were used to construct two active shape models (right lung and left lung) which were then used for image segmentation. The algorithm was validated in 20 patients, comparing its results to reference delineation of corresponding CT images, and by comparing automatic segmentation to manual delineations in SPECT images. RESULTS: The Dice coefficient between automatic SPECT delineations and manual SPECT delineations were 0.83 ± 0.04% for the right and 0.82 ± 0.05% for the left lung. There was statistically significant difference between reference volumes from CT and automatic delineations for the right (R = 0.53, p = 0.02) and left lung (R = 0.69, p < 0.001) in SPECT. There were similar observations when comparing reference volumes from CT and manual delineations in SPECT images, left lung (bias was - 10 ± 491, R = 0.60, p = 0.005) right lung (bias 36 ± 524 ml, R = 0.62, p = 0.004). CONCLUSION: Automated segmentation on SPECT images are on par with manual segmentation on SPECT images. Relative large volumetric differences between manual delineations of functional SPECT images and anatomical CT images confirms that lung segmentation of functional SPECT images is a challenging task. The current algorithm is a first step towards automatic quantification of wide range of measurements.

V/P SPECT as a diagnostic tool for pregnant women with suspected pulmonary embolism.

PURPOSE: The purpose of the study was to assess the prevalence of pulmonary embolism (PE) and other lung diseases among pregnant women with suspected PE and to calculate the radiation exposure to patient and fetus in this population. As a secondary aim, we evaluated the negative predictive value of a normal ventilation/perfusion single photon emission computed tomography (V/P SPECT) examination in pregnancy. METHODS: We studied all 127 pregnant women who had suspected PE and had undergone V/P SPECT at our institution in the course of a 5-year period. Radiation exposure to patient and fetus and the negative predictive value of a normal V/P SPECT examination were also measured. RESULTS: V/P SPECT identified PE in 11 women (9%). Moreover, in 15 women (12%) the examination revealed pneumonia (in 2 cases in addition to PE) and in 1 woman signs of airway obstruction were revealed. Among the 116/127 women (91%) where PE was ruled out by V/P SPECT, none was diagnosed subsequently with PE or deep venous thrombosis (DVT) during the same pregnancy or puerperal period. For P SPECT, the calculated fetal absorbed dose was < 0.6 mGy,and the calculated breast absorbed dose 0.6 mGy. For V SPECT, the calculated fetal absorbed dose was < 0.014 mGy and the breast absorbed dose 0.25 mGy. CONCLUSION: The prevalence of PE was low (9%) among pregnant women with suspected disease. Pneumonia was diagnosed in 12% of patients. The negative predictive value of V/P SPECT was high, and the radiation exposure from V/P SPECT was low both for fetus and patient.

The added value of hybrid ventilation/perfusion SPECT/CT in patients with stable COPD or apparently healthy smokers. Cancer-suspected CT findings in the lungs are common when hybrid imaging is used.

Ventilation/perfusion (V/P) single-photon emission computed tomography (SPECT) is recognized as a diagnostic method with potential beyond the diagnosis of pulmonary embolism. V/P SPECT identifies functional impairment in diseases such as heart failure (HF), pneumonia, and chronic obstructive pulmonary disease (COPD). The development of hybrid SPECT/computed tomography (CT) systems, combining functional with morphological imaging through the addition of low-dose CT (LDCT), may be useful in COPD, as these patients are prone to lung cancer and other comorbidities. The aim of this study was to investigate the added value of LDCT among healthy smokers and patients with stable COPD, when examined with V/P SPECT/CT hybrid imaging. Sixty-nine subjects, 55 with COPD (GOLD I-IV) and 14 apparently healthy smokers, were examined with V/P SPECT and LDCT hybrid imaging. Spirometry was used to verify COPD grade. Only one apparently healthy smoker and three COPD patients had a normal or nearly normal V/P SPECT. All other patients showed various degrees of airway obstruction, even when spirometry was normal. The same interpretation was reached on both modalities in 39% of the patients. LDCT made V/P SPECT interpretation more certain in 9% of the patients and, in 52%, LDCT provided additional diagnoses. LDCT better characterized the type of emphysema in 12 patients. In 19 cases, tumor-suspected changes were reported. Three of these 19 patients (ie, 4.3% of all subjects) were in the end confirmed to have lung cancer. The majority of LDCT findings were not regarded as clinically significant. V/P SPECT identified perfusion patterns consistent with decompensated left ventricular HF in 14 COPD patients. In 16 patients (23%), perfusion defects were observed. HF and perfusion defects were not recognized with LDCT. In COPD patients and long-time smokers, hybrid imaging had added value compared to V/P SPECT alone, by identifying patients with lung malignancy and more clearly identifying emphysema. V/P SPECT visualizes comorbidities to COPD not seen with LDCT, such as pulmonary embolism and left ventricular HF.

Grading obstructive lung disease using tomographic pulmonary scintigraphy in patients with chronic obstructive pulmonary disease (COPD) and long-term smokers.

UNLABELLED: The severity of chronic obstructive lung disease (COPD) is defined by the degree of flow limitation measured as forced expiratory volume in 1 s, which mainly reflects impairment of large and intermediate airways. However, COPD is primarily a small airways disease. Therefore, better diagnostic tools are needed. Ventilation-Perfusion (V/P) SPECT is a sensitive method to detect obstructive lung changes but criteria for staging airway obstruction are missing. PURPOSE: To define and validate criteria to stage COPD using V/P SPECT. METHOD: 74 subjects (healthy non-smokers, healthy smokers or with stable COPD) were included. All were examined with V/P SPECT in a hybrid SPECT/CT system. Spirometry was performed and patients were evaluated with the clinical COPD questionnaire (CCQ). V/P SPECT was interpreted independently. Preserved lung function (%) was evaluated. The degree of airway obstruction on V/P SPECT was graded according to newly-developed grading criteria. The degree of airway obstruction was graded from normal (0) to severe (3). The airway obstructivity-grade and degree of preserved lung function were compared to GOLD, CCQ and LDCT emphysema extent. RESULTS: Obstructivity-grade (r = 0.66, P < 0.001) and the degree of preserved lung function (r = -0.70, P < 0.001) both correlated to GOLD. Total preserved lung function decreased in relation to higher GOLD stage. There was a significant difference between healthy controls and apparently healthy long time smokers both regarding obstructivity-grade (P = 0.001) and preserved lung function (P < 0.001). Long-time smokers did not differ significantly from GOLD 1 COPD patients (P = 0.14 and P = 0.55 for obstructivity-grade and preserved lung function, respectively). However, patients in GOLD 1 differed in obstructivity-grade from non-smoking controls (P = 0.02). CONCLUSION: Functional imaging with V/P SPECT enables standardized grading of airway obstruction as well as reduced lung function, both of which correlate with GOLD stage. V/P SPECT shows that long-term smokers in most cases have signs of ventilatory impairment and airway obstruction not shown by spirometry.

Impact of ventilation/perfusion single-photon emission computed tomography on treatment duration of pulmonary embolism.

PURPOSE: The aim of the study was to establish whether the duration of anticoagulant (AC) therapy can be tailored, on an objective basis, by using ventilation/perfusion single-photon emission computed tomography (V/P SPECT) and to assess the extent of residual perfusion defects over time. In particular, we addressed the following: (a) is the extent of perfusion recovery at 3 months of initial pulmonary embolism (PE) diagnosis a satisfactory criterion for deciding the duration of oral AC? (b) Is it safe to withdraw AC at 3 months if perfusion recovery is complete? PATIENTS AND METHODS: Of 269 consecutive patients with suspected PE, 100 patients were diagnosed with PE using V/P SPECT. Sixty-seven patients with acute PE were followed up clinically and with V/P SPECT at 3 months. Sixty-four patients were subject to review and examination using V/P SPECT for a period of 6 months and 33 were followed up only clinically. Therapy was terminated after 3 months if perfusion was normalized, and patients were free of symptoms and the risk of hypercoagulability. Initial extension of PE did not have an impact on decision making. RESULTS: PE extension varied from 10 to 70% in the acute stage. After 3 months, complete resolution of PE was found in 48 patients. The treating pulmonologist decided to terminate therapy in 35 (73%) patients and to continue AC in 13 patients because of persistent risk factors. Six months later, at the second control stage, 53 patients had complete recovery of pulmonary perfusion. Eleven patients still had perfusion defects at 6 months. No recurrence was identified at 6 months in the 35 patients whose therapy was terminated after 3 months. No bleeding effects were observed in any of the patients during the 6-month follow-up. CONCLUSION: This study shows that AC therapy can be tailored, on an objective basis, by using V/P SPECT. Normalization of perfusion at 3 months of initial PE diagnosis was a reliable indicator that AC could be safely withdrawn in patients who were without hypercoagulability risk.

Perfusion SPECT in patients with suspected pulmonary embolism.

PURPOSE: Ventilation/perfusion tomography (V/PSPECT), with new interpretation criteria and newer tracers for ventilation imaging, has markedly improved the diagnostic yield in acute pulmonary embolism (PE). Here, we evaluated the diagnostic performance of perfusion SPECT (PSPECT) without ventilation imaging. METHODS: We studied 152 patients with clinically suspected PE who had been examined with both V/PSPECT and multidetector computed tomographic angiography (MD-CTA). The diagnosis or exclusion of PE was decided by the referring clinician based on both the V/PSPECT and/or MD-CTA findings in combination with the clinical findings. PSPECT images were retrospectively examined by a physician with experience in the interpretation of planar perfusion scans who was blinded to clinical, V/PSPECT and MD-CTA data. PSPECT images were interpreted without the aid of chest radiography. All the patients who were deemed to have PE were given anticoagulant therapy. RESULTS: Of the 152 patients, 59 (39%) received a final diagnosis of PE, and 19 (32%) had associated cardiopulmonary diseases such as pneumonia, COPD, or left heart failure. PSPECT correctly identified 53 (90%) of the 59 patients with PE. The specificity was 88 of 93 (95%). None of the PSPECT images was rated nondiagnostic. PSPECT yielded an overall diagnostic accuracy of 93% (95% confidence interval, CI, 87-96%). At the observed PE prevalence of 39 %, the positive and negative predictive values of PSPECT were 91% (95% CI, 80-97%) and 94% (95% CI, 86-97%), respectively. CONCLUSION: In managing critically ill patients, PSPECT might be a valid alternative to V/PSPECT or MD-CTA since it was able to identify most patients with PE with a low false-positive rate and no inconclusive results.

The value of tomographic ventilation/perfusion scintigraphy (V/PSPECT) for follow-up and prediction of recurrence in pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is diagnosed with imaging techniques such as ventilation/perfusion (V/P) lung scintigraphy or multidetector computed tomography of the pulmonary arteries (MDCT). Lung scintigraphy can be performed with planar (V/P PLANAR) and tomographic (V/P SPECT) techniques. V/P SPECT has higher sensitivity and specificity than V/P PLANAR. As nephrotoxic contrast media are not used during V/P SPECT, examinations can be repeated for evaluation of resolution of perfusion defects after PE. However, the value of residual perfusion defects identified using V/P SPECT for the prediction of recurrent PE has not been thoroughly evaluated. MATERIAL AND METHODS: We evaluated resolution and recurrence of PE in 227 patients (mean age 63 ± 17 years, 134[59%] women) with PE undergoing ≥ 2 SPECT examinations in 2005-2007. PE was defined as minor (<20% perfusion defect on SPECT, n=86), medium (20-50% perfusion defect on SPECT, n=99), or major (>50% perfusion defect on SPECT, n=42). RESULTS: At second V/P SPECT examination, complete resolution of perfusion defects had occurred in 45 (52%) patients with minor PE after 8.2 ± 7.4 months, in 29 (29%) of patients with medium PE after 6.2 ± 5.9 months, and in 2(5%) of patients with major PE after 6.5 ± 0.7 months. During 47 ± 24 months of follow up, 37(16 %) patients suffered recurrent PE. Of these 37, 34 (92%) showed residual perfusion defects at the second V/P SPECT examination. Recurrence of PE was also predicted by advanced age and female gender. However, in multivariate regression analysis, recurrence was only predicted by age (p=0.0013) and residual perfusion defect on V/P SPECT (p=0.0039). CONCLUSION: In conclusion, complete resolution of PE was common in patients with minor PE, whereas residual perfusion defects were widespread in patients with medium and major PE. PE patients identified with persistent perfusion defects at follow-up SPECT have a high risk of PE recurrence.

Ventilation/Perfusion SPECT for Diagnosis of Pulmonary Embolism and Other Diseases.

V/P(SPECT) has the potential to become a first hand tool for diagnosis of pulmonary embolism based on standardized technology and new holistic interpretation criteria. Pretest probability helps clinicians choose the most appropriate objective test for diagnosis or exclusion of PE. Interpretation should also take into account all ventilation and perfusion patterns allowing diagnosis of other cardiopulmonary diseases than PE. In such contexts, V/P(SPECT) has excellent sensitivity and specificity. Nondiagnostic reports are ≤3%. V/P(SPECT) has no contraindication; it is noninvasive and has very low radiation exposure. Moreover, acquisition time for V/P(SPECT) is only 20 minutes. It allows quantification of PE extension which has an impact on individual treatment. It is uniquely useful for followup and research.

Tomographic ventilation/perfusion lung scintigraphy in the monitoring of the effect of treatment in pulmonary embolism: serial follow-up over a 6-month period.

BACKGROUND: Pulmonary embolism (PE) is a severe condition with nonspecific symptoms. Diagnosis relies on medical imaging but follow-up is currently based on clinical symptoms and general risk factors. The duration of anticoagulant treatment after an acute episode of PE is still subject to debate and the best method of identifying the risk of recurrence in individual patients is undefined. Tomographic lung scintigraphy [ventilation/perfusion single photon emission computed tomography (V/P SPECT)] has improved the diagnostic accuracy with regard to PE but has not been evaluated for PE follow-up. AIM: The aim of this prospective study was to quantitatively follow the natural history of treated PE using V/P SPECT, which could prove helpful in defining an anticoagulant treatment regime for individual patients. METHODS: Of 83 consecutive patients with clinically suspected PE examined with V/P SPECT, 23 patients with confirmed PE were followed by serial V/P SPECT examinations over a 6-month period. All patients were also followed clinically. RESULTS: The mean relative decrease in PE extent compared with the time of diagnosis was 54±26% at 2 weeks, 79±30% at 3 months, and 82±30% at 6 months. Significant resolution of mismatched perfusion defects occurred between V/P SPECT controls within the first 3 months of anticoagulation (P<0.001) but not thereafter. V/P SPECT identified four patients with chronic PE, even though all patients were free from symptoms at 3-month follow-up. CONCLUSION: Follow-up of PE with V/P SPECT is feasible to evaluate treatment effectiveness in individual patients and to identify patients that develop chronic PE. This study also confirms that resolution of perfusion defects after PE occurs within the first 3 months of treatment. It is therefore recommended that V/P SPECT follow-up should be considered at 3 months after diagnosis.