Pulmonary Ventilation Imaging Research Articles

Hyperpolarized 129Xe MRI and spectroscopy of gas-exchange abnormalities in bilateral lung transplant recipients

BACKGROUNDThere is currently no sensitive, non-invasive method of screening for chronic lung allograft dysfunction (CLAD), the primary barrier to long-term survival after lung transplant. Conventional pulmonary function testing is imprecise absent a sustained decline. Hyperpolarized 129Xe MRI is a sensitive tool for 3D imaging of regional pulmonary ventilation and gas exchange abnormalities and may aid in early detection of CLAD. METHODSAdult patients post bilateral lung transplant were screened for CLAD based on the ISHLT criteria. Those with established allografts (n=10) underwent 129Xe gas exchange MRI and spectroscopy and were compared to results from 16 young healthy volunteers and 16 age-matched healthy volunteers. One lung transplant recipient was excluded from final data analysis due to a concurrent lung infection found incidentally after MRI. Imaging provided quantitative maps of the ventilation defect percent (VDP), membrane high percent, and RBC defect percent. Spectroscopy yielded RBC/membrane ratio, oxygenation-dependent RBC shift, and RBC oscillation amplitude. RESULTSThe analysis included nine lung transplant recipients, seven with CLAD and two without. CLAD patients exhibited VDP values consistent with their FEV1 decline (rho=0.79, p=0.048). Hemoglobin-corrected RBC transfer was reduced in all transplant recipients vs. young healthy controls (median [first quartile–third quartile] of 13% [9%-22%] vs 2% [1.75%-3%], P=0.003) as well as vs. age-matched controls (5.5% [2% - 9.25%], p=0.039). Spectroscopy demonstrated reduced RBC/membrane signal (0.26 [0.17-0.31] vs. 0.62 [0.50-0.66], p< 0.001 and vs. 0.48 [0.42-0.55], p = 0.002), reduced RBC chemical shift (217.4 [217.2-217.7]ppm vs 218.2 [218.0-218.5]ppm, p=0.009 and vs. 218.3 [218.2-218.5]ppm, p=0.003), and increased RBC oscillation amplitude vs. the young healthy controls (14.1% [12.2%-16.4%] vs 11.1% [9.9%-11.9%], p=0.003). CONCLUSIONSPatients with CLAD exhibited significant ventilation defects that correlated with FEV1 decline, that, along with RBC transfer defects and other 129Xe gas exchange and hemodynamic abnormalities, could provide a promising means of early detection of physiological changes in patients with CLAD.

Perfusion imaging heterogeneity during NO inhalation distinguishes pulmonary arterial hypertension (PAH) from healthy subjects and has potential as an imaging biomarker

BackgroundWithout aggressive treatment, pulmonary arterial hypertension (PAH) has a 5-year mortality of approximately 40%. A patient’s response to vasodilators at diagnosis impacts the therapeutic options and prognosis. We hypothesized that analyzing perfusion images acquired before and during vasodilation could identify characteristic differences between PAH and control subjects.MethodsWe studied 5 controls and 4 subjects with PAH using HRCT and 13NN PET imaging of pulmonary perfusion and ventilation. The total spatial heterogeneity of perfusion (CV2Qtotal) and its components in the vertical (CV2Qvgrad) and cranio-caudal (CV2Qzgrad) directions, and the residual heterogeneity (CV2Qr), were assessed at baseline and while breathing oxygen and nitric oxide (O2 + iNO). The length scale spectrum of CV2Qr was determined from 10 to 110 mm, and the response of regional perfusion to O2 + iNO was calculated as the mean of absolute differences. Vertical gradients in perfusion (Qvgrad) were derived from perfusion images, and ventilation-perfusion distributions from images of 13NN washout kinetics.ResultsO2 + iNO significantly enhanced perfusion distribution differences between PAH and controls, allowing differentiation of PAH subjects from controls. During O2 + iNO, CV2Qvgrad was significantly higher in controls than in PAH (0.08 (0.055–0.10) vs. 6.7 × 10–3 (2 × 10–4–0.02), p < 0.001) with a considerable gap between groups. Qvgrad and CV2Qtotal showed smaller differences: − 7.3 vs. − 2.5, p = 0.002, and 0.12 vs. 0.06, p = 0.01. CV2Qvgrad had the largest effect size among the primary parameters during O2 + iNO. CV2Qr, and its length scale spectrum were similar in PAH and controls. Ventilation-perfusion distributions showed a trend towards a difference between PAH and controls at baseline, but it was not statistically significant.ConclusionsPerfusion imaging during O2 + iNO showed a significant difference in the heterogeneity associated with the vertical gradient in perfusion, distinguishing in this small cohort study PAH subjects from controls.

Deriving Pulmonary Ventilation Images From Clinical 4D-CBCT Using a Deep Learning-Based Model.

PurposeThe current algorithms for measuring ventilation images from 4D cone-beam computed tomography (CBCT) are affected by the accuracy of deformable image registration (DIR). This study proposes a new deep learning (DL) method that does not rely on DIR to derive ventilation images from 4D-CBCT (CBCT-VI), which was validated with the gold-standard single-photon emission-computed tomography ventilation image (SPECT-VI).Materials and MethodsThis study consists of 4D-CBCT and 99mTc-Technegas SPECT/CT scans of 28 esophagus or lung cancer patients. The scans were rigidly registered for each patient. Using these data, CBCT-VI was derived using a deep learning-based model. Two types of model input data are studied, namely, (a) 10 phases of 4D-CBCT and (b) two phases of peak-exhalation and peak-inhalation of 4D-CBCT. A sevenfold cross-validation was applied to train and evaluate the model. The DIR-dependent methods (density-change-based and Jacobian-based methods) were used to measure the CBCT-VIs for comparison. The correlation was calculated between each CBCT-VI and SPECT-VI using voxel-wise Spearman’s correlation. The ventilation images were divided into high, medium, and low functional lung regions. The similarity of different functional lung regions between SPECT-VI and each CBCT-VI was evaluated using the dice similarity coefficient (DSC). One-factor ANONA model was used for statistical analysis of the averaged DSC for the different methods of generating ventilation images.ResultsThe correlation values were 0.02 ± 0.10, 0.02 ± 0.09, and 0.65 ± 0.13/0.65 ± 0.15, and the averaged DSC values were 0.34 ± 0.04, 0.34 ± 0.03, and 0.59 ± 0.08/0.58 ± 0.09 for the density change, Jacobian, and deep learning methods, respectively. The strongest correlation and the highest similarity with SPECT-VI were observed for the deep learning method compared to the density change and Jacobian methods.ConclusionThe results showed that the deep learning method improved the accuracy of correlation and similarity significantly, and the derived CBCT-VIs have the potential to monitor the lung function dynamic changes during radiotherapy.

Dynamic susceptibility contrast 19 F-MRI of inhaled perfluoropropane: a novel approach to combined pulmonary ventilation and perfusion imaging.

PurposeTo assess alveolar perfusion by applying dynamic susceptibility contrast MRI to 19F‐MRI of inhaled perfluoropropane (PFP). We hypothesized that passage of gadolinium‐based contrast agent (GBCA) through the pulmonary microvasculature would reduce magnetic susceptibility differences between water and gas components of the lung, elevating the T2∗ of PFP.MethodsLung‐representative phantoms were constructed of aqueous PFP‐filled foams to characterize the impact of aqueous/gas phase magnetic susceptibility differences on PFP T2∗. Aqueous phase magnetic susceptibility was modulated by addition of different concentrations of GBCA. In vivo studies were performed to measure the impact of intravenously administered GBCA on the T2∗ of inhaled PFP in mice (7.0 Tesla) and in healthy volunteers (3.0 Tesla).ResultsPerfluoropropane T2∗ was sensitive to modulation of magnetic susceptibility difference between gas and water components of the lung, both in phantom models and in vivo. Negation of aqueous/gas phase magnetic susceptibility difference was achieved in lung‐representative phantoms and in mice, resulting in a ~2 to 3× elevation in PFP T2∗ (3.7 to 8.5 ms and 0.7 to 2.6 ms, respectively). Human studies demonstrated a transient elevation of inhaled PFP T2∗ (1.50 to 1.64 ms) during passage of GBCA bolus through the lung circulation, demonstrating sensitivity to lung perfusion.ConclusionWe demonstrate indirect detection of a GBCA in the pulmonary microvasculature via changes to the T2∗ of gas phase PFP within directly adjacent alveoli. This approach holds potential for assessing alveolar perfusion by dynamic susceptibility contrast 19F‐MRI of inhaled PFP, with concurrent assessment of lung ventilation properties, relevant to lung physiology and disease.

Fast and accurate reconstruction of human lung gas MRI with deep learning.

To fast and accurately reconstruct human lung gas MRI from highly undersampled k-space using deep learning. The scheme was comprised of coarse-to-fine nets (C-net and F-net). Zero-filling images from retrospectively undersampled k-space at an acceleration factor of 4 were used as input for C-net, and then output intermediate results which were fed into F-net. During training, a L2 loss function was adopted in C-net, while a function that united L2 loss with proton prior knowledge was used in F-net. The 871 hyperpolarized 129 Xe pulmonary ventilation images from 72 volunteers were randomly arranged as training (90%) and testing (10%) data. Ventilation defect percentage comparisons were implemented using a paired 2-tailed Student's t-test and correlation analysis. Furthermore, prospective acquisitions were demonstrated in 5 healthy subjects and 5 asymptomatic smokers. Each image with size of 96 × 84 could be reconstructed within 31 ms (mean absolute error was 4.35% and structural similarity was 0.7558). Compared with conventional compressed sensing MRI, the mean absolute error decreased by 17.92%, but the structural similarity increased by 6.33%. For ventilation defect percentage, there were no significant differences between the fully sampled and reconstructed images through the proposed algorithm (P = 0.932), but had significant correlations (r = 0.975; P < 0.001). The prospectively undersampled results validated a good agreement with fully sampled images, with no significant differences in ventilation defect percentage but significantly higher signal-to-noise ratio values. The proposed algorithm outperformed classical undersampling methods, paving the way for future use of deep learning in real-time and accurate reconstruction of gas MRI.

An image reconstruction algorithm for electrical impedance tomography using Symkaczmarz based on structured sparse representation

Electrical impedance tomography (EIT) is a new medical imaging technology that is used to estimate changes in the internal conductivity based on measurements of the border voltage disturbance. However, the generalized inverse operator of image reconstruction for EIT is ill-posed and ill-conditioned. In order to improve reconstruction quality, the structured sparse representation is integrated into the iterative process of the Symkaczmarz algorithm for EIT image reconstruction in this paper. The sparsity prior and the underlying structure characteristics of conductivity reconstruction are considered in the proposed algorithm. Both simulation and experiment results indicate that the proposed method has feasibility for pulmonary ventilation imaging and great potential for improving the image quality.

A Feasibility Study of Single-inhalation, Single-energy Xenon-enhanced CT for High-resolution Imaging of Regional Lung Ventilation in Humans

The objective of this study was to assess the feasibility of single-inhalation xenon-enhanced computed tomography (XeCT) to provide clinically practical, high-resolution pulmonary ventilation imaging to clinics with access to only a single-energy computed tomography scanner, and to reduce the subject's overall exposure to xenon by utilizing a higher (70%) concentration for a much shorter time than has been employed in prior studies. We conducted an institutional review board-approved prospective feasibility study of XeCT for 15 patients undergoing thoracic radiotherapy. For XeCT, we acquired two breath-hold single-energy computed tomography images of the entire lung with a single inhalation each of 100% oxygen and a mixture of 70% xenon and 30% oxygen, respectively. A video biofeedback system for coached patient breathing was used to achieve reproducible breath holds. We assessed the technical success of XeCT acquisition and side effects. We then used deformable image registration to align the breath-hold images with each other to accurately subtract them, producing a map of lung xenon distribution. Additionally, we acquired ventilation single-photon emission computed tomography-computed tomography (V-SPECT-CT) images for 11 of the 15 patients. For a comparative analysis, we partitioned each lung into 12 sectors, calculated the xenon concentration from the Hounsfield unit enhancement in each sector, and then correlated this with the corresponding V-SPECT-CT counts. XeCT scans were tolerated well overall, with a mild (grade 1) dizziness as the only side effect in 5 of the 15 patients. Technical failures in five patients occurred because of inaccurate breathing synchronization with xenon gas delivery, leaving seven patients analyzable for XeCT and single-photon emission computed tomography correlation. Sector-wise correlations were strong (Spearman coefficient >0.75, Pearson coefficient >0.65, P value <.002) for two patients for whom ventilation deficits were visibly pronounced in both scans. Correlations were nonsignificant for the remaining five who had more homogeneous XeCT ventilation maps, as well as strong V-SPECT-CT imaging artifacts attributable to airway deposition of the aerosolized imaging agent. Qualitatively, XeCT demonstrated higher resolution and no central airway deposition artifacts compared to V-SPECT-CT. In this pilot study, single-breath XeCT ventilation imaging was generally feasible for patients undergoing thoracic radiotherapy, using an imaging protocol that is clinically practical and potentially widely available. In the future, the xenon delivery failures can be addressed by straightforward technical improvements to the patient biofeedback coaching system.

Pulmonary ventilation imaging in asthma and cystic fibrosis using oxygen-enhanced 3D radial ultrashort echo time MRI.

A previous study demonstrated the feasibility of using 3D radial ultrashort echo time (UTE) oxygen-enhanced MRI (UTE OE-MRI) for functional imaging of healthy human lungs. The repeatability of quantitative measures from UTE OE-MRI needs to be established prior to its application in clinical research. To evaluate repeatability of obstructive patterns in asthma and cystic fibrosis (CF) with UTE OE-MRI with isotropic spatial resolution and full chest coverage. Volunteer and patient repeatability. Eighteen human subjects (five asthma, six CF, and seven normal subjects). Respiratory-gated free-breathing 3D radial UTE (80 μs) sequence at 1.5T. Two 3D radial UTE volumes were acquired sequentially under normoxic and hyperoxic conditions. A subset of subjects underwent repeat acquisitions on either the same day or ≤15 days apart. Asthma and CF subjects also underwent spirometry. A workflow including deformable registration and retrospective lung density correction was used to compute 3D isotropic percent signal enhancement (PSE) maps. Median PSE (MPSE) and ventilation defect percent (VDP) of the lung were measured from the PSE map. The relations between MPSE, VDP, and spirometric measures were assessed using Spearman correlations. The test-retest repeatability was evaluated using Bland-Altman analysis and intraclass correlation coefficients (ICC). Ventilation measures in normal subjects (MPSE = 8.0%, VDP = 3.3%) were significantly different from those in asthma (MPSE = 6.0%, P = 0.042; VDP = 21.7%, P = 0.018) and CF group (MPSE = 4.5%, P = 0.0006; VDP = 27.2%, P = 0.002). MPSE correlated significantly with forced expiratory lung volume in 1 second percent predicted (ρ = 0.72, P = 0.017). The ICC of the test-retest VDP and MPSE were both ≥0.90. In all subject groups, an anterior/posterior gradient was observed with higher MPSE and lower VDP in the posterior compared to anterior regions (P ≤ 0.0021 for all comparisons). 3D radial UTE OE-MRI supports quantitative differentiation of diseased vs. healthy lungs using either whole lung VDP or MPSE with excellent test-retest repeatability. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1287-1297.

Incorporating Pulmonary Ventilation Imaging for Functional Avoidance of the Lung in Radiation Treatment Planning

Incorporating Pulmonary Ventilation Imaging for Functional Avoidance of the Lung in Radiation Treatment Planning

SU‐C‐202‐06: Design and Development of a Non‐Rigid Phantom Ventilating Air Quantitatively Evaluating CT‐Based Pulmonary Ventilation Imaging

Purpose:A validation study using human or sheep for CT pulmonary ventilation (CT‐V) imaging are inefficient and partially unstable. In this study, we designed and developed non‐rigid phantom ventilating air to quantitatively evaluate the CT‐V image.Methods:The phantom consisted of an acryl cylinder filled with polyurethane foam designed to pulmonic alveoli and a polyurethane membrane was attached to the inferior end of the phantom to simulate a lung diaphragm. Also, trachea‐shaped polyurethane tubes were covered by the foam and the tubes passed through the outside in order to exchange a gas. Lung arteries were also modeled with polyurethane and were located adjacent to the trachea model. Two 3D‐CT scans were performed at exhale and inhale using an air contrast agent of xenon gas, respectively. The exhale 3D‐CT was deformed to the inhale 3D‐CT using the in‐house program with the NiftyReg. Sixteen landmarks were assigned around trachea and lung arteries in the inhale image and the deformed exhale image. Target Registration Error (TRE) for each landmark between the two images was calculated for commissioning of our program. CT‐V image was generated using Jacobian determinant metrics (JD). Subsequently, HU value change between the two images was measured. The correlation coefficient was calculated between the JD and the HU change.Results:The deformable and ventilation phantom shows a variety of displacement for each landmark (1 mm − 20 mm). The mean TRE was 4.5 ± 4.7 mm (Maximum: 12.3 mm). The relationship between the JD and the HU change shows high correlation. (R = −0.86). At the several landmarks where TRE values were over 3 mm, the correlation was poor.Conclusion:The phantom may be a useful QA tool to validate CT‐V imaging. We will improve our deformable image registration program for CT‐V imaging with the efficient way using the phantom.

MRI methods for pulmonary ventilation and perfusion imaging

Separate assessment of respiratory mechanics, gas exchange and pulmonary circulation is essential for the diagnosis and therapy of pulmonary diseases. Due to the global character of the information obtained clinical lung function tests are often not sufficiently specific in the differential diagnosis or have a limited sensitivity in the detection of early pathological changes. The standard procedures of pulmonary imaging are computed tomography (CT) for depiction of the morphology as well as perfusion/ventilation scintigraphy and single photon emission computed tomography (SPECT) for functional assessment. Magnetic resonance imaging (MRI) with hyperpolarized gases, O2-enhanced MRI, MRI with fluorinated gases and Fourier decomposition MRI (FD-MRI) are available for assessment of pulmonary ventilation. For assessment of pulmonary perfusion dynamic contrast-enhanced MRI (DCE-MRI), arterial spin labeling (ASL) and FD-MRI can be used. Imaging provides a more precise insight into the pathophysiology of pulmonary function on a regional level. The advantages of MRI are a lack of ionizing radiation, which allows a protective acquisition of dynamic data as well as the high number of available contrasts and therefore accessible lung function parameters. Sufficient clinical data exist only for certain applications of DCE-MRI. For the other techniques, only feasibility studies and case series of different sizes are available. The clinical applicability of hyperpolarized gases is limited for technical reasons. The clinical application of the techniques described, except for DCE-MRI, should be restricted to scientific studies.

Feasibility of human lung ventilation imaging using highly polarized naturally abundant xenon and optimized three-dimensional steady-state free precession.

To demonstrate the potential for high quality MRI of pulmonary ventilation using naturally abundant xenon (NAXe) gas. MRI was performed at 1.5 Tesla (T) and 3 T on one healthy smoker and two healthy never-smokers. 129Xe gas was polarized to ∼25% using an in-house spin-exchange optical pumping polarizer fitted with a laser diode array with integrated volume holographic grating and optical train system. Volunteers inhaled 1 L of NAXe for an 8 to 15 s breathhold while MR images were acquired with full-lung coverage using a three-dimensional steady-state free precession sequence, optimized for maximum signal-to-noise ratio (SNR) at a given spatial resolution. For the purpose of image quality comparison, the MR acquisition was repeated at 1.5 T with 400 mL enriched xenon and 200 mL 3He. All NAXe lung images were of high quality, with mean SNRs of 25-40 (voxel 4.2 × 4.2 × 8/10 mm3) and ∼30% improvement at 3 T versus 1.5 T. The high SNR permitted identification of minor ventilation defects in the healthy smoker's lungs. NAXe images were of comparable SNR to those obtained with enriched xenon and 3He. Optimization of MR pulse sequences and advances in polarization technology have facilitated high quality pulmonary ventilation imaging with inexpensive NAXe gas.

Beam orientation optimization of pulmonary ventilation image-guided intensity modulated radiotherapy for lung cancer

Objective To evaluate the dosimetric advantage of pulmonary ventilation image guided intensity-modulated radiotherapy (IMRT) planning in protecting functional lung with optimizing beam orientation. Methods Sixteen non-small cell lung cancer patients were included and carried out with the peak-exhale and peak-inhale CT scans, respectively. The two sets of CT images were then input to the pulmonary ventilation analysis system to acquire the three dimensional distribution of ventilation images. Then the area of better pulmonary ventilation named as functional lung was delineated automatically by the system. The pulmonary ventilation images were fused with CT images by using treatment planning system. Two kinds of IMRT plans were generated, in cluding conventional IMRT, in which the main dose constraints were applied to total lung, as well as f-IMRT, with the main dose constraints applying to functional lung. To evaluate the dosimetric changes of beam arrangement, the five equal-spaced beams and five manual optimization beams were applied to each plan. The dosimetric difference between IMRT and f-IMRT plans was compared using the paired t-test. Result In the same category of plan, all the dosimetric parameters of PTV had no significant difference (P>0.05) in the plan with FMOB, comparing with FESB. The dose delivered to spinal cord, esophagus, and heart varied in degrees, whereas only the dosimetric difference of the mean dose to esophagus and V60 to heart had statistically significance (t =4.33, -2.37, P <0.05) between the plan with FESB and plan with FMOB. For IMRT plans, compared with FESB, the volume of functional lung at more than 5, 10 and 20 Gy (FLV5, FLV10, and FLV20) decreased significantly in plan with FMOB (t=4.87, 4.74, 2.33, P <0.05). The FLV5, FLV10, and FLV20 in plan with FESB were (54.2±29.1)%, (42.5±22.1)%, (26.3±20.7)%, respectively, while in plan with FMOB were (30.2±18.5)%, (24.1±12.0)%, (17.8±8.9)%, respectively. For f-IMRT plans, compared the plan with FMOB to plan with FESB, the FLV5, FLV10, and FLV20 of the functional lung decreased significantly (t=5.30, 4.84, 2.23, P <0.05). The FLV5, FLV10, and FLV20 were (52.4±20.7)%, (37.1±12.2)%, (21.1±5.8)%, respectively in plan with FESB, while in plan with FMOB were (29.2±18.3)%, (23.0±14.8)%, (16.7±9.7)%, respectively. The dosimetric parameters of low-dose region of total lung also decreased in different degrees, with statistical significance (t=7.96-6.07, P <0.05). Conclusions The combination of pulmonary ventilation images and IMRT, with further optimizing the beam directions, can effectively reduce the radiation dose on functional lung, which is expected to reduce the incidence and severity of radiation pneumonitis and might improve the NSCLC patient′s quality of life. Key words: Lung neoplasms/radiotherapy; Four-dimensional computed tomography; Pulmonary ventilation; Plan optimization

Pulmonary Ventilation Imaging Based on 4-Dimensional Computed Tomography: Comparison With Pulmonary Function Tests and SPECT Ventilation Images

4-dimensional computed tomography (4D-CT)-based pulmonary ventilation imaging is an emerging functional imaging modality. The purpose of this study was to investigate the physiological significance of 4D-CT ventilation imaging by comparison with pulmonary function test (PFT) measurements and single-photon emission CT (SPECT) ventilation images, which are the clinical references for global and regional lung function, respectively. In an institutional review board-approved prospective clinical trial, 4D-CT imaging and PFT and/or SPECT ventilation imaging were performed in thoracic cancer patients. Regional ventilation (V4DCT) was calculated by deformable image registration of 4D-CT images and quantitative analysis for regional volume change. V4DCT defect parameters were compared with the PFT measurements (forced expiratory volume in 1 second (FEV1; % predicted) and FEV1/forced vital capacity (FVC; %). V4DCT was also compared with SPECT ventilation (VSPECT) to (1) test whether V4DCT in VSPECT defect regions is significantly lower than in nondefect regions by using the 2-tailed t test; (2) to quantify the spatial overlap between V4DCT and VSPECT defect regions with Dice similarity coefficient (DSC); and (3) to test ventral-to-dorsal gradients by using the 2-tailed t test. Of 21 patients enrolled in the study, 18 patients for whom 4D-CT and either PFT or SPECT were acquired were included in the analysis. V4DCT defect parameters were found to have significant, moderate correlations with PFT measurements. For example, V4DCT(HU) defect volume increased significantly with decreasing FEV1/FVC (R=-0.65, P<.01). V4DCT in VSPECT defect regions was significantly lower than in nondefect regions (mean V4DCT(HU) 0.049 vs 0.076, P<.01). The average DSCs for the spatial overlap with SPECT ventilation defect regions were only moderate (V4DCT(HU)0.39 ± 0.11). Furthermore, ventral-to-dorsal gradients of V4DCT were strong (V4DCT(HU) R(2) = 0.69, P=.08), which was similar to VSPECT (R(2) = 0.96, P<.01). An 18-patient study demonstrated significant correlations between 4D-CT ventilation and PFT measurements as well as SPECT ventilation, providing evidence toward the validation of 4D-CT ventilation imaging.

High-resolution imaging of pulmonary ventilation and perfusion with 68Ga-VQ respiratory gated (4-D) PET/CT

Our group has previously reported on the use of (68)Ga-ventilation/perfusion (VQ) PET/CT scanning for the diagnosis of pulmonary embolism. We describe here the acquisition methodology for (68)Ga-VQ respiratory gated (4-D) PET/CT and the effects of respiratory motion on image coregistration in VQ scanning. A prospective study was performed in 15 patients with non-small-cell lung cancer. 4-D PET and 4-D CT images were acquired using an infrared marker on the patient's abdomen as a surrogate for breathing motion following inhalation of Galligas and intravenous administration of (68)Ga-macroaggregated albumin. Images were reconstructed with phase-matched attenuation correction. The lungs were contoured on CT and PET VQ images during free-breathing (FB) and at maximum inspiration (Insp) and expiration (Exp). The similarity between PET and CT volumes was measured using the Dice coefficient (DC) comparing the following groups; (1) FB-PET/CT, (2) InspPET/InspCT, (3) ExpPET/Exp CT, and (4) FB-PET/AveCT. A repeated measures one-way ANOVA with multiple comparison Tukey tests were performed to evaluate any difference between the groups. Diaphragmatic motion in the superior-inferior direction on the 4-D CT scan was also measured. 4-D VQ scanning was successful in all patients without additional acquisition time compared to the nongated technique. The highest volume overlap was between ExpPET and ExpCT and between FB-PET and AveCT with a DC of 0.82 and 0.80 for ventilation and perfusion, respectively. This was significantly better than the DC comparing the other groups (0.78-0.79, p < 0.05). These values agreed with a visual inspection of the images with improved image coregistration around the lung bases. The diaphragmatic motion during the 4-D CT scan was highly variable with a range of 0.4-3.4cm (SD 0.81cm) in the right lung and 0-2.8cm (SD 0.83cm) in the left lung. Right-sided diaphragmatic nerve palsy was observed in 3 of 15 patients. (68)Ga-VQ 4-D PET/CT is feasible and the blurring caused by respiratory motion is well corrected with 4-D acquisition, which principally reduces artefact at the lung bases. The images with the highest spatial overlap were the combined expiration phase or FB PET and average CT. With higher resolution than SPECT/CT, the PET/CT technique has a broad range of potential clinical applications including diagnostic algorithms for patients with suspected pulmonary embolism, preoperative evaluation of regional lung function and improving assessment or understanding of pulmonary physiology in the vast range of pulmonary diseases.

Application value of pulmonary perfusion and ventilation imaging during diagnosis and treatment of pulmonary embolism

肺通气灌注(V/Q)显像于20世纪60年代末进入临床,是成熟的诊断肺栓塞影像学检查.它通过直接显示肺动脉阻塞导致的肺组织血流灌注缺损而诊断肺栓塞,确定肺栓塞的部位、范围.和传统平面V/Q显像相比,新近发展的V/Q断层显像(V/QSPECT)诊断肺栓塞的准确性更高,定位、定量更精确,可发现更多的外周型肺栓塞病灶;其诊断肺栓塞的敏感度为96％～99％,特异度为91％～98％[1-4]。

WE‐G‐214‐09: Validation of 4D‐CT Pulmonary Ventilation Imaging: Characterization of the Reproducibility

Purpose: A novel ventilation imaging method based on 4D‐CT has been applied to functional radiotherapy planning and assessing radiation‐induced ventilation changes. Understanding of its reproducibility is a prerequisite for such applications, however it has not been studied to date. The purpose of this study is to develop a method for validating 4D‐CT ventilation imaging through characterizing its reproducibility and show preliminary results. Methods: 4D‐CT ventilation images were created for three patients from repeat 4D‐CT scans at different time points, including two pre‐treatment (pre‐RT1 and pre‐RT2), one mid‐treatment (mid‐RT) and/or one post‐treatment (post‐RT). The reference (pre‐RT1) was compared with pre‐RT2 to quantify the temporal change in the absence of therapeutic intervention. Pre‐RT1 was also compared with mid‐RT and/or post‐RT to quantify the temporal change in the presence of therapeutic intervention. Finally, the Spearmanˈs voxel‐based correlations between pre‐RT1 and pre‐RT2 were compared to those between pre‐RT1 and mid‐RT or post‐RT to investigate the hypothesis: the temporal change in the absence of therapeutic intervention is smaller than that in the presence of therapeutic intervention. Results: Differences between the temporal changes in the absence and presence of therapeutic intervention were inconsistent. Regions of both agreement and disagreement were identified throughout the lung between pre‐RT1 and pre‐RT2, mid‐RT or post‐RT. The correlations with pre‐RT2 (absence) (range, 0.41–0.64) were slightly higher than or comparable to those with mid‐RT or post‐RT (presence) (range, 0.42–0.62). In general, the ventilation variations between pre‐RT1 and pre‐RT2 increased with increasing respiratory variations during the 4D‐CT acquisition. Conclusions: Preliminary results from a 3‐patient study suggest inconsistent differences between the temporal changes of 4D‐CT ventilation in the absence and presence of therapeutic intervention. Respiratory variations have been found to contribute to deteriorate the reproducibility. Ongoing studies focus on investigating more patients and spatial characteristics of the temporal changes.SK, JB and CL are employees of Philips Research Europe.

WE‐G‐214‐06: Pulmonary Ventilation and Perfusion Imaging Using 4DCT

Purpose: To develop a functional imaging technique that can simultaneously detect changes in lung ventilation and lung perfusion using 4D‐CT. This high‐resolution functional information can be incorporated in a treatment planning to minimize the dose to highly functional areas of the lung, and can also be used to assess the efficacy of treatment post radiation therapy. Methods: Recently, a technique was presented to estimate lung ventilation using 4DCT by detecting the changes in CT characteristics of the pulmonary parenchyma. We go a step further and develop the theory to extract not only regional fractional changes in ventilation but also fractional changes in mass that may be indicative of blood flow. Changes in lung ventilation are estimated by applying a mass correction that is estimated using the ratio of the global inhale‐mass and end‐exhale mass. Changes in lung perfusion are indicated by changes in “apparent mass”. Changes in “apparent mass” are estimated by applying a volume correction that is estimated using the ratio of global inhale volume and end‐exhale volume. In both the cases a subtraction of the corrected images is performed by spatially matching the images at each phase of the respiratory cycle. Spatial matching is carried out using a deformable image registration algorithm. Results: Preliminary studies indicate a linear relationship between the mass‐corrected fractional changes in volume and global measurement of tidal volume changes (slope = 1.01, R‐square = 0.97). A similar slightly linear relationship is observed between the volume‐corrected fractional changes in “apparent mass” and global measurement of mass (slope = 1.21, R‐square = 0.75). Conclusions: The technique presented above can extract both changes in ventilation and “apparent mass” that maybe indicative of perfusion simultaneously from a single set of 4DCT images. It however remains to the shown that these changes correspond to perfusion (future studies).

Investigation of four-dimensional computed tomography-based pulmonary ventilation imaging in patients with emphysematous lung regions

A pulmonary ventilation imaging technique based on four-dimensional (4D) computed tomography (CT) has advantages over existing techniques. However, physiologically accurate 4D-CT ventilation imaging has not been achieved in patients. The purpose of this study was to evaluate 4D-CT ventilation imaging by correlating ventilation with emphysema. Emphysematous lung regions are less ventilated and can be used as surrogates for low ventilation. We tested the hypothesis: 4D-CT ventilation in emphysematous lung regions is significantly lower than in non-emphysematous regions. Four-dimensional CT ventilation images were created for 12 patients with emphysematous lung regions as observed on CT, using a total of four combinations of two deformable image registration (DIR) algorithms: surface-based (DIRsur) and volumetric (DIRvol), and two metrics: Hounsfield unit (HU) change (VHU) and Jacobian determinant of deformation (VJac), yielding four ventilation image sets per patient. Emphysematous lung regions were detected by density masking. We tested our hypothesis using the one-tailed t-test. Visually, different DIR algorithms and metrics yielded spatially variant 4D-CT ventilation images. The mean ventilation values in emphysematous lung regions were consistently lower than in non-emphysematous regions for all the combinations of DIR algorithms and metrics. VHU resulted in statistically significant differences for both DIRsur (0.14 ± 0.14 versus 0.29 ± 0.16, p = 0.01) and DIRvol (0.13 ± 0.13 versus 0.27 ± 0.15, p < 0.01). However, VJac resulted in non-significant differences for both DIRsur (0.15 ± 0.07 versus 0.17 ± 0.08, p = 0.20) and DIRvol (0.17 ± 0.08 versus 0.19 ± 0.09, p = 0.30). This study demonstrated the strong correlation between the HU-based 4D-CT ventilation and emphysema, which indicates the potential for HU-based 4D-CT ventilation imaging to achieve high physiologic accuracy. A further study is needed to confirm these results.

Four‐dimensional computed tomography pulmonary ventilation images vary with deformable image registration algorithms and metrics

A novel pulmonary ventilation imaging technique based on four-dimensional (4D) CT has advantages over existing techniques and could be used for functional avoidance in radiotherapy. There are various deformable image registration (DIR) algorithms and two classes of ventilation metric that can be used for 4D-CT ventilation imaging, each yielding different images. The purpose of this study was to quantify the variability of the 4D-CT ventilation to DIR algorithms and metrics. 4D-CT ventilation images were created for 12 patients using different combinations of two DIR algorithms, volumetric (DIR(vol)) and surface-based (DIR(sur)), yielding two displacement vector fields (DVFs) per patient (DVF(voI) and DVF(sur)), and two metrics, Hounsfield unit (HU) change (V(HU)) and Jacobian determinant of deformation (V(Jac)), yielding four ventilation image sets (V(HU)(vol), V(HU)(sur), V(Jac)(voI), and V(Jac)(sur). First DVF(vol) and DVF(sur) were compared visually and quantitatively to the length of 3D displacement vector difference. Second, four ventilation images were compared based on voxel-based Spearman's rank correlation coefficients and coefficients of variation as a measure of spatial heterogeneity. V(HU)(vol) was chosen as the reference for the comparison. The mean length of 3D vector difference between DVF(vol) and DVF(sur) was 2.0 +/- 1.1 mm on average, which was smaller than the voxel dimension of the image set and the variations. Visually, the reference V(HU)(vol) demonstrated similar regional distributions with V(HU)(sur); the reference, however, was markedly different from V(Jac)(vol) and V((Jac)(sur). The correlation coefficients of V(HU)(vol) with V(HU)(sur), V(Jac)(vol) and V(Jac)(sur) were 0.77 +/- 0.06, 0.25 +/- 0.06 and 0.15 +/- 0.07, respectively, indicating that the metric introduced larger variations in the ventilation images than the DIR algorithm. The spatial heterogeneities for V(HU)(vol), 'V(HU)(sur), V(Jac)(vol), and V(Jac)(sur) were 1.8 +/- 1.6, 1.8 +/- 1.5 (p = 0. 85), 0.6 +/- 0.2 (p = 0.02), and 0.7 +/- 0.2 (p = 0.03), respectively, also demonstrating that the metric introduced larger variations. 4D-CT pulmonary ventilation images vary widely with DIR algorithms and metrics. Careful physiologic validation to determine the appropriate DIR algorithm and metric is needed prior to its applications.