Potential of Gd-DTPA-mannan liposome particles as a pulmonary perfusion MRI contrast agent: an initial animal study

Suga K, Mikawa M, Ogasawara N, et al. Potential of Gd-DTPA-mannan liposome particles as a pulmonary perfusion MRI contrast agent: An initial animal study. Invest Radiol 2001;36:136-145.RATIONALE AND OBJECTIVES: A paramagnetic, particle-type MR contrast agent, (Gd-diethylenetriamine pentaacetic acid [DTPA]-mannan-cholesterol)-coated liposomes, was designed to localize in the lung by the mechanism of capillary blockade, and the potential of this agent for pulmonary perfusion MRI was experimentally investigated. METHODS: Before and up to 60 minutes after slow injection of this contrast agent, MR images were sequentially acquired at 10-second intervals along the same transaxial plane of the lung by using a gradient-echo pulse sequence with a short echo time of 1.2 ms on a 1.5-T MR scanner. After the minimal dose for obtaining a sufficient lung enhancement effect was determined in five rabbits, the time course of the enhancement effect was evaluated in six dogs by arterial blood gas analysis. The efficacy of MRI for detecting perfusion defects was evaluated in seven other dogs with pulmonary embolism. RESULTS: Normal lungs were dose-dependently enhanced by this agent, and with a 2.0 mL/kg dose, dependent lungs were enhanced by more than 201%, with an average half-life of the enhancement effect of 35.7 +/- 5.3 minutes. With less than this dose (1.0-1.5 mL/kg), all of the embolized lung portions were clearly identified as perfusion defects. The prolonged enhancement effect allowed the acquisition of subsequent multisectional lung images, thus facilitating the assessment of anatomic location and extent of the perfusion defects. The reduction of PaO2 in room air after injection was within 5 mm Hg in both normal and embolized animals. CONCLUSIONS: These initial, experimental results show that paramagnetically labeled liposome particles may be a successful MR contrast agent for pulmonary perfusion imaging.     

低剂量与常规剂量对比剂双能量肺灌注图像质量对比分析

目的:探讨对比剂剂量对双源CT双能量肺灌注成像质量的影响.方法:疑肺动脉栓塞患者行双源CT双能量肺灌注扫描,30例使用低剂量(0.7ml/kg)对比剂,30例使用常规剂量对比剂(1.5ml/kg),注射速率均为4.5ml/s.扫描后同时获得肺动脉CTA及肺灌注图像.测量左、右叶肺动脉干及各肺叶动脉增强后的CT值,对比分析两组间增强后的CT值.判断肺灌注图像质量并分级,比较两组的肺灌注图像质量差异.结果:低剂量组与常规剂量组左、右叶肺动脉干及各肺叶动脉增强后的CT值无明显差异(P＞0.05).肺段及亚段肺动脉图像清晰显示.低剂量组肺灌注图像大部分信号均匀(26/30),常规剂量组肺灌注图像大部分信号均匀(24/30).常规剂量组上腔静脉、右心房高密度对比剂所致灌注伪影明显多于低剂量组(48:10).结论:低剂量与常规剂量双能量肺灌注成像的肺动脉图像质量无明显差异,降低对比剂剂量可以减少双能量肺灌注图像的伪影.     

Quantitative evaluation of MR perfusion imaging using blood pool contrast agent in subjects without pulmonary diseases and in patients with pulmonary embolism

Objective

To assess the feasibility of time-resolved parallel three-dimensional magnetic resonance imaging (MRI) for quantitative analysis of pulmonary perfusion using a blood pool contrast agent.

Methods

Quantitative perfusion analysis was performed using novel software to assess pulmonary blood flow (PBF), pulmonary blood volume (PBV) and mean transit time (MTT) in a quantitative manner.

Results

The evaluation of lung perfusion in the normal subjects showed an increase of PBF, PBV ventrally to dorsally (gravitational direction), and the highest values at the upper lobe, with a decrease to the middle and lower lobe (isogravitational direction). MTT showed no relevant changes in either the gravitational or isogravitational directions. In comparison with normally perfused lung areas (in diseased patients), the pulmonary embolism (PE) regions showed a significantly lower mean PBF (20?±?0.6?ml/100?ml/min, normal region 94?±?1?ml/100?ml/min; P?P?P?Conclusion Our results demonstrate the feasibility of using time-resolved dynamic contrast-enhanced MRI to determine normal range and regional variation of pulmonary perfusion and perfusion deficits in patients with PE.

Key Points

? Recently introduced blood pool contrast agents improve MR evaluation of lung perfusion ? Regional differences in lung perfusion indicating a gravitational and isogravitational dependency. ? Focal areas of significantly decreased perfusion are detectable in pulmonary embolism.     

Magnetic resonance imaging detection of an experimental pulmonary perfusion deficit using a macromolecular contrast agent. Polylysine-gadolinium-DTPA40.

RATIONALE AND OBJECTIVES. This study was designed to evaluate the potential of a blood-pool magnetic resonance (MR) contrast agent, polylysine-gadolinium-DTPA40 (polylysine-Gd-DTPA40) for detecting pulmonary perfusion defects. MATERIALS AND METHODS. Pulmonary emboli were induced in 10 rats by venous injection of 0.2 mL of air. Axial spin-echo images were acquired (TR = 800 mseconds; TE = 6 mseconds) before and after air injection and serially after the administration of polylysine-Gd-DTPA40. The embolism model was confirmed by scintigraphy using 99mTc-macroaggregated albumin. RESULTS. Signal intensity differences between normal and embolized lungs before and after the air injection were less than 25%. After polylysine-Gd-DTPA40 administration, signal intensity of the perfused lung increased more than 200%, whereas the embolized lung increased by only 25%. Signal intensities of the perfused lung remained stable for 1 hour, whereas signal intensities of the embolized lung gradually increased for 20 minutes as the air embolus dissolved. CONCLUSION. Magnetic resonance imaging (MRI) enhanced with a macromolecular blood-pool contrast agent can be used to detect acute pulmonary embolism in a confirmed animal model.     

Lung ventilation‐ and perfusion‐weighted Fourier decomposition magnetic resonance imaging: In vivo validation with hyperpolarized 3He and dynamic contrast‐enhanced MRI

The purpose of this work was to validate ventilation‐weighted (VW) and perfusion‐weighted (QW) Fourier decomposition (FD) magnetic resonance imaging (MRI) with hyperpolarized ³He MRI and dynamic contrast‐enhanced perfusion (DCE) MRI in a controlled animal experiment. Three healthy pigs were studied on 1.5‐T MR scanner. For FD MRI, the VW and QW images were obtained by postprocessing of time‐resolved lung image sets. DCE acquisitions were performed immediately after contrast agent injection. ³He MRI data were acquired following the administration of hyperpolarized helium and nitrogen mixture. After baseline MR scans, pulmonary embolism was artificially produced. FD MRI and DCE MRI perfusion measurements were repeated. Subsequently, atelectasis and air trapping were induced, which followed with FD MRI and ³He MRI ventilation measurements. Distributions of signal intensities in healthy and pathologic lung tissue were compared by statistical analysis. Images acquired using FD, ³He, and DCE MRI in all animals before the interventional procedure showed homogeneous ventilation and perfusion. Functional defects were detected by all MRI techniques at identical anatomical locations. Signal intensity in VW and QW images was significantly lower in pathological than in healthy lung parenchyma. The study has shown usefulness of FD MRI as an alternative, noninvasive, and easily implementable technique for the assessment of acute changes in lung function. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Laser-polarized (3)He as a probe for dynamic regional measurements of lung perfusion and ventilation using magnetic resonance imaging.

Magnetic resonance imaging (MRI) using laser-polarized noble gases, such as (129)Xe and (3)He, allows unparalleled noninvasive information on gas distribution in lung airways and distal spaces. In addition to pulmonary ventilation, lung perfusion assessment is crucial for proper diagnosis of pathological conditions, such as pulmonary embolism. Magnetic resonance perfusion imaging usually can be performed using techniques based on the detection of water protons in tissues. However, lung proton imaging is extremely difficult due to the low proton density and the magnetically inhomogeneous structure of the lung parenchyma. Here we show that laser-polarized (3)He can be used as a noninvasive probe to image, in a single MRI experiment, not only the ventilation but also the perfusion state of the lungs. Blood volume maps of the lungs were generated based on the (3)He signal depletion during the first pass of a superparamagnetic contrast agent bolus. The combined and simultaneous lung ventilation and perfusion assessments are demonstrated in normal rat lungs and are applied to an experimental animal model of pulmonary embolism. Magn Reson Med 44:1-4, 2000.     

Chronische Lungenembolie – Radiologische Bildmorphologie und Differenzialdiagnose

In chronic pulmonary embolism branches of the pulmonary arterial tree remain partially or totally occluded. This may lead to pulmonary hypertension with the development of right ventricular hypertrophy as well as structural changes of pulmonary arteries. Imaging of chronic pulmonary embolism should prove vessel occlusions (pulmonary angiography, MSCT, MRI) and reduction of regional lung perfusion (lung scanning, MSCT, MRI). According to current guidelines ventilation-perfusion lung scanning and pulmonary angiography are still recommended as the methods of choice. MSCT and MRI provide technical alternatives which are helpful in differential diagnosis versus other types of pulmonary hypertension. In spite of medical and surgical measures (in rare cases pulmonary thromboendarterectomy) the prognosis of chronic pulmonary embolism remains unfavourable.     

Pulmonary disorders: ventilation-perfusion MR imaging with animal models

PURPOSE: To demonstrate the capability of magnetic resonance (MR) imaging to assess alteration in regional pulmonary ventilation and perfusion with animal models of airway obstruction and pulmonary embolism. MATERIALS AND METHODS: Airway obstruction was created by inflating a 5-F balloon catheter into a secondary bronchus. Pulmonary emboli were created by injecting thrombi into the inferior vena cava. Regional pulmonary ventilation was assessed with 100% oxygen as a T1 contrast agent. Regional pulmonary perfusion was assessed with a two-dimensional fast low-angle shot, or FLASH, sequence with short repetition and echo times after intravenous administration of gadopentetate dimeglumine. RESULTS: Matched ventilation and perfusion abnormalities were identified in all animals with airway obstruction. MR perfusion defects without ventilation abnormalities were seen in all animals with pulmonary emboli. CONCLUSION: Ventilation and perfusion MR imaging are able to provide regional pulmonary functional information with high spatial and temporal resolution. The ability of MR imaging to assess both the magnitude and regional distribution of pulmonary functional impairment could have an important effect on the evaluation of lung disease.     

磁共振成像对肺动脉栓塞血流动力学的评价

目的:探讨增强磁共振肺灌注成像对肺动脉栓塞血流动力学改变的价值。材料和方法:经放射性核素肺通气-灌注显像和MR肺灌注成像(MRPP)诊断的20例肺动脉栓塞患者和14例健康志愿者,行主肺动脉MR血流编码扫描,通过分析肺实质的信号强度变化率(TROS)、时间-信号曲线、右/左心室内径比及主肺动脉的相关参数(主肺动脉直径、血流峰值、平均流速、单位时间内流量等),比较肺动脉栓塞患者与志愿者间肺动脉血流动力学参数间的差异,评价MR在肺动脉栓塞血流动力学方面的作用。结果:肺栓塞患者组与健康志愿者组肺实质信号强度变化率、峰值时间、主肺动脉直径、右/左心室内径比差异有显著性意义;两组间的主肺动脉峰值流速、平均流速、流量具有统计学差异,肺栓塞患者MR血流编码的肺动脉峰值流速-时间曲线表现为收缩期峰值流时间提前,并可见明显反流。结论:MRI具有诊断肺动脉栓塞的可行性,并可测量肺动脉血流动力学参数变化,粗略估计肺动脉高压程度,有望成为一种研究肺栓塞的无创性影像方法。     

Contrast-enhanced MR imaging of the lung: assessments of ventilation and perfusion.

The use of aerosolized gadopentetate dimeglumine to define regional lung ventilation and of intravenously administered polylysine-(gadopentetate dimeglumine)40 to assess regional lung perfusion was investigated. In 10 healthy rats who breathed aerosolized gadopentetate dimeglumine (0.25 mol/L) for 5 minutes, pulmonary signal intensity increased diffusely in both lungs by more than 70%. When the same animals received intravenously administered polylysine-(gadopentetate dimeglumine)40 (0.1 mmol of gadolinium per kilogram), there was an additional 300% enhancement of the pulmonary parenchyma. In a rat model of acute unilateral pulmonary embolism (n = 5), perfusion defects were identified after administration of polylysine-(gadopentetate dimeglumine)40, but no ventilation abnormality was seen after inhalation of gadopentetate dimeglumine. In a rat model of acute unilateral airway obstruction (n = 5), only the ventilated right lung enhanced after inhalation of gadopentetate dimeglumine. In four of these animals, the focal ventilation defect was accompanied by a matched decrease in perfusion, seen after enhancement of the blood pool with polylysine-(gadopentetate dimeglumine)40.     

MR Diagnosis of a Pulmonary Embolism: Comparison of P792 and Gd-DOTA for First-Pass Perfusion MRI and Contrast-Enhanced 3D MRA in a Rabbit Model

Objective

To compare P792 (gadomelitol, a rapid clearance blood pool MR contrast agent) with gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA), a standard extracellular agent, for their suitability to diagnose a pulmonary embolism (PE) during a first-pass perfusion MRI and 3D contrast-enhanced (CE) MR angiography (MRA).

Materials and Methods

A perfusion MRI or CE-MRA was performed in a rabbit PE model following the intravenous injection of a single dose of contrast agent. The time course of the pulmonary vascular and parenchymal enhancement was assessed by measuring the signal in the aorta, pulmonary artery, and lung parenchyma as a function of time to determine whether there is a significant difference between the techniques. CE-MRA studies were evaluated by their ability to depict the pulmonary vasculature and following defects between 3 seconds and 15 minutes after a triple dose intravenous injection of the contrast agents.

Results

The P792 and Gd-DOTA were equivalent in their ability to demonstrate PE as perfusion defects on first pass imaging. The signal from P792 was significantly higher in vasculature than that from Gd-DOTA between the first and the tenth minutes after injection. The results suggest that a CE-MRA PE could be reliably diagnosed up to 15 minutes after injection.

Conclusion

P792 is superior to Gd-DOTA for the MR diagnosis of PE.     

Perfusion CT in patients with advanced bronchial carcinomas: a novel chance for characterization and treatment monitoring?

Advanced bronchial carcinomas by means of perfusion and peak enhancement using dynamic contrast-enhanced multislice CT are characterized. Twenty-four patients with advanced bronchial carcinoma were examined. During breathhold, after injection of a contrast-medium (CM), 25 scans were performed (1 scan/s) at a fixed table position. Density-time curves were evaluated from regions of interest of the whole tumor and high- and low-enhancing tumor areas. Perfusion and peak enhancement were calculated using the maximum-slope method of Miles and compared with size, localization (central or peripheral) and histology. Perfusion of large tumors (>50 cm³) averaged over both the whole tumor (P=0.001) and the highest enhancing area (P=0.003) was significantly lower than that of smaller ones. Independent of size, central carcinomas had a significantly (P=0.04) lower perfusion (mean 27.9 ml/min/100 g) than peripheral ones (mean 66.5 ml/min/100 g). In contrast, peak enhancement of central and peripheral carcinomas was not significantly different. Between non-small-cell lung cancers and small-cell lung cancers, no significant differences were observed in both parameters. In seven tumors, density increase after CM administration started earlier than in the aorta, indicating considerable blood supply from pulmonary vessels. Tumor perfusion was dependent on tumor size and localization, but not on histology. Furthermore, perfusion CT disclosed blood supply from both pulmonary and/or bronchial vessels in some tumors.Abbreviations AIF arterial input function - CT computed tomography - CM contrast media - ROI region of interest - SCLC small-cell lung cancer - NSCLC non-small-cell lung cancer - SD standard deviation     

3D pulmonary perfusion MRI and MR angiography of pulmonary embolism in pigs after a single injection of a blood pool MR contrast agent

The purpose of this study was to assess the feasibility of contrast-enhanced 3D perfusion MRI and MR angiography (MRA) of pulmonary embolism (PE) in pigs using a single injection of the blood pool contrast Gadomer. PE was induced in five domestic pigs by injection of autologous blood thrombi. Contrast-enhanced first-pass 3D perfusion MRI (TE/TR/FA: 1.0 ms/2.2 ms/40°; voxel size: 1.3×2.5×4.0 mm³; TA: 1.8 s per data set) and high-resolution 3D MRA (TE/TR/FA: 1.4 ms/3.4 ms/40°; voxel size: 0.8×1.0×1.6 mm³) was performed during and after a single injection of 0.1 mmol/kg body weight of Gadomer. Image data were compared to pre-embolism Gd-DTPA-enhanced MRI and post-embolism thin-section multislice CT (n=2). SNR measurements were performed in the pulmonary arteries and lung. One animal died after induction of PE. In all other animals, perfusion MRI and MRA could be acquired after a single injection of Gadomer. At perfusion MRI, PE could be detected by typical wedge-shaped perfusion defects. While the visualization of central PE at MRA correlated well with the CT, peripheral PE were only visualized by CT. Gadomer achieved a higher peak SNR of the lungs compared to Gd-DTPA (21±8 vs. 13±3). Contrast-enhanced 3D perfusion MRI and MRA of PE can be combined using a single injection of the blood pool contrast agent Gadomer.     

Computed tomography densitometry of the lung: a method to assess perfusion defects in acute pulmonary embolism

OBJECTIVE: To evaluate the potential of spiral computed tomography (CT) densitometry of the lung to assess segmental perfusion defects in patients with acute pulmonary embolism. MATERIALS AND METHODS: Ten patients with known segmental or lobar perfusion defects on ventilation/perfusion scintigraphy and with normal findings in the contralateral lung segment underwent spiral CT of the thorax before and after the administration of contrast material. Regions of interest were defined in 14 segments with normal perfusion and in 14 segments with reduced perfusion. Three consecutive densitometry measurements were performed in each segment. RESULTS: Those segments with reduced perfusion showed a significantly lower mean CT value on the enhanced scans (-813.4 +/- 57.1 Hounsfield units (HU) vs -794.0 +/- 44.8 HU, P = 0.01) and a significantly decreased contrast enhancement (12.3 +/- 18.2 HU vs 29.8 +/- 16.6 HU, P <0.01) when compared to segments with normal perfusion. Measurements from the unenhanced CT scans were not statistically different between segments with reduced and normal perfusion. CONCLUSIONS: Spiral CT densitometry allows the assessment of at least segmental perfusion defects in patients with acute pulmonary embolism.     

Prediction of postoperative pulmonary function using perfusion magnetic resonance imaging of the lung

PURPOSE: To assess semiquantitatively the regional distribution of lung perfusion using magnetic resonance (MR) perfusion imaging.MATERIALS AND METHODS: Subjects were 20 consecutive patients with bronchogenic carcinoma, who underwent MR imaging (MRI) and radionuclide (RN) perfusion scans for preoperative evaluation. Three-dimensional (3D) images of whole lungs were obtained before and 7 seconds after bolus injection of contrast material (5 ml of Gd-DTPA). Subtraction images were constructed from these dynamic images. Lung areas enhanced with the contrast material were measured and multiplied by changes in signal intensity, summed for the whole lung, and the right-to-left lung ratios were calculated. The predicted postoperative forced expiratory volume in 1 second (FEV1) was estimated using MR and RN perfusion ratios.RESULTS: The correlation between perfusion ratios derived from the MR and RN studies was excellent (r = 0.92). Sixteen of 20 patients underwent surgery, and 12 patients had postoperative pulmonary function tests. The predicted FEV1 derived from the MR perfusion ratio correlated well with the postoperative FEV1 in the 12 patients (r = 0.68).CONCLUSION: Perfusion MRI is suitable for semiquantitative evaluation of regional pulmonary perfusion.     

A large intra-atrial thrombus detected during a lung perfusion scan with technetium-99m macroaggregated albumin injected through the subclavian venous line

A sixty five year old female patient carrying a double lumen subclavian catheter, with severe right-sided heart failure, was subjected to lung perfusion scan in order to rule out pulmonary embolism. Administration of Tc-99m macroaggregate albumin ((99m)Tc-MAA), via a double lumen (Hickman) subclavian line, resulted in trapping almost half of the injected dose in the right atrium, at the tip of the subclavian catheter. There was no evidence of pulmonary embolism. This finding was interpreted as consistent with the presence of a large intra-atrial thrombus. This thrombus, despite the thrombolytic treatment that followed, was detached and caused cardiac arrest and eventually the death of the patient. Autopsy showed a massive pulmonary embolus. This report suggests, that injecting (99m)Tc-MAA for a lung perfusion study via the central venous line, may result in the early detection of a thrombus, as in this case at the tip of the catheter and this may be life saving for the patient. We have been unable to find in the literature a similar case of a thrombus detected by the iv administration of (99m)Tc-MAA.     

MRT der akuten Lungenembolie

Recent technical developments have substantially improved the potential of MRI for the diagnosis of pulmonary embolism. On the MR scanner side this includes the development of short magnets and dedicated whole-body MRI systems, which allow a comprehensive evaluation of pulmonary embolism and deep venous thrombosis in a single exam. The introduction of parallel imaging has substantially improved the spatial and temporal resolution of pulmonary MR angiography. By combining time-resolved pulmonary perfusion MRI with high-resolution pulmonary MRA a sensitivity and specificity of over 90% is achievable, which is comparable to the accuracy of CTA. Thus, for certain patient groups, such as patients with contraindications to iodinated contrast media and young women with a low clinical probability for pulmonary embolism, MRI can be considered as a first-line imaging tool for the assessment of pulmonary embolism.     

Perfusion magnetic resonance imaging of the lung: characterization of pneumonia and chronic obstructive pulmonary disease. A feasibility study

Perfusion magnetic resonance (MR) imaging is a promising new method for detection of perfusion defects in the diagnosis of pulmonary embolism. In the present study we evaluated the first-pass characteristics of perfusion MR imaging in patients with pneumonia or chronic obstructive pulmonary disease (COPD), frequent differential diagnoses to pulmonary embolism. Dynamic contrast-enhanced MR images of 12 patients with acute pneumonia and 13 patients with exacerbation of COPD were acquired in both the coronal and transaxial planes (an inversion recovery prepared gradient-echo sequence using 0.05 mmol/kg gadodiamide/injection). The MR images and the signal intensity (SI) versus time curves were characterized for each disease entity and compared with normal lung and the findings in pulmonary embolism from our previous study. The perfusion MR images of pneumonia showed distinct regions of increased contrast enhancement; in COPD with signs of emphysema (11 of the 13 COPD patients), the images showed a coarse pattern of reduced contrast enhancement. The SI versus time curves of pneumonia, COPD with signs of emphysema, and normal lung were statistically different, the respective pooled SI values (+/-95% CI) being as follows: mean baseline SI, 20.7 (1.1), 7.4 (0.4), and 8.5 (0.3); mean peak SI, no peak, 12.9 (1.5), and 27 (4.6); and mean max change of SI in percent, 110 (27), 79 (22), and 205 (52). Perfusion MR imaging of pneumonia and COPD with signs of emphysema showed first-pass that were characteristics promising for diagnostic use. Both the MR images and the SI versus time curves were different from the perfusion characteristics in normal lung and pulmonary embolism shown previously.     

The use of iridium-191m for pulmonary blood flow imaging

A preliminary evaluation of the potential utilisation of osmium-191/iridium-191m for pulmonary blood flow imaging was performed. This evaluation was part of a more general study concerning the use of ^191mIr for first-pass radionuclide angiocardiography (FPRNA). In eight selected patients with suspected pulmonary disease, we generated, from the data collected during FPRNA, an image representing blood flow distribution to the lungs. A software program was developed in order to differentiate the lungs from the heart, to define the wash-in lung phase and finally to construct an image representing pulmonary blood flow distribution. We compared that image with a standard lung perfusion image using technetium-99m macroaggregated albumin (MAA) and plain chest X-ray and computerized tomography (CT). The obtained ^191mIr perfusion images showed a spatial activity distribution similar to that seen on ^99mTc-MAA lung perfusion scans, and in most cases the same perfusion defects. Disease revealed by plain chest X-ray and CT was nicely correlated with perfusion defects seen on the ^191mIr images. The combined information of lung perfusion and dynamic cardiac parameters obtained by FPRNA (right and left ventricular ejection fractions) added another relevant dimension to the clinical picture of patients with pulmonary embolism, chronic obstructive lung disease, lung tumour or suspected congestive heart failure. We conclude that ^191mIr may become a practical tool for achieving the conceptually promising approach of combined lung-heart real-time imaging. Correspondence to: M. Bocher     

Multislice computed tomography perfusion imaging for visualization of acute pulmonary embolism: animal experience

The purpose of our animal study was to evaluate a new computed tomography (CT) subtraction technique for visualization of perfusion defects within the lung parenchyma in subsegmental pulmonary embolism (PE). Seven healthy pigs were entered into a prospective trial. Acute PE was artificially induced by fresh clot material prior to the CT scans. Within a single breath-hold, whole thorax CT scans were performed with a 16-slice multidetector-row CT scanner (SOMATOM Sensation 16; Siemens, Forchheim, Germany) before and after intravenous application of 80 ml of contrast medium with a flow rate of 4 ml/s, followed by a saline chaser. The scan parameters were 120 kV and 100 mAs_eff, using a thin collimation of 16×0.75 mm and a table speed/rotation of 15–18 mm (pitch, 1.25–1.5; rotation time, 0.5 s). Axial source images were reconstructed with an effective slice thickness of 1 mm (overlap, 30%). A new automatic subtraction technique was used. After 3D segmentation of the lungs in the plain and contrast-enhanced series, threshold-based extraction of major airways and vascular structures in the contrast images was performed. This segmentation was repeated in the plain CT images segmenting the same number of vessels and airways as in the contrast images. Both scans were registered onto each other using nonrigid registration. After registration both image sets were filtered in a nonlinear fashion excluding segmented airways and vessels. After subtracting the plain CT data from the contrast data the resulting enhancement images were color-encoded and overlaid onto the contrast-enhanced CT angiography (CTA) images. This color-encoded combined display of parenchymal enhancement of the lungs was evaluated interactively on a workstation (Leonardo, Siemens) in axial, coronal and sagittal plane orientations. Axial contrast-enhanced CTA images were rated first, followed by an analysis of the combination images. Finally, CTA images were reread focusing on areas with perfusion deficits indicating PE on the color-coded enhancement display. Subtraction was feasible for all seven studies. In one animal, opacification of the pulmonary arteries was suboptimal owing to heart insufficiency. In the remaining six pigs, a total of 37 perfusion defects were clearly assessable downstream of occluded subsegmental arteries, showing lower or missing enhancement compared with normally perfused lung parenchyma. Indeterminate findings from CTA showed typical PE perfusion defects in four out of six cases on CT subtraction. Additionally, 22 peripheral triangular-shaped enhancement defects were delineated. Nine of these findings were reclassified as definitely being caused by PE on second reading of the CTA data sets. Our initial results have shown that this new subtraction technique for perfusion imaging of PE is feasible, using routine contrast delivery. Dedicated examination protocols are mandatory for adequate opacification of the pulmonary arteries and for optimization of data sets for subsequent subtraction. Perfusion imaging allows a comprehensive assessment of morphology and function, providing more accurate information on acute PE.This paper contains data on behalf of the Amersham Health Research Fellowship Grant, ECR 2003.