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Physical examination is the standard diagnostic approach for adult inguinal hernias. We aimed to evaluate the clinical utility of routine preoperative computed tomography scans in the prone position for predicting intractable cases of inguinal hernias before performing transabdominal preperitoneal repairs. We retrospectively analyzed 56 lesions in 48 patients with inguinal hernias who underwent prone computed tomography scans prior to transabdominal preperitoneal repairs. To assess the ability of prone computed tomography to enable the accurate preoperative diagnosis of inguinal hernias, we compared preoperative hernia types as classified through hernia computed tomography and intraoperative diagnosis. We also analyzed the relationship between operation time and hernia type in unilateral cases (n = 40). The overall hernia computed tomography detection and classification accuracy rates were 81.0% and 83.9%, respectively, using the Japan Hernia Society classification system (2009 version) and 84.3% and 91.2%, respectively, using the European Hernia Society classification system. There were no differences in the hernia type frequencies between the shorter (n = 20) and longer (n = 20) operation time groups. Two patients had sliding inguinal hernias with prolapsing bladders, both of which were detectable using preoperative prone computed tomography. Although transabdominal preperitoneal repairs were completed in both cases, the operation times were exceptionally long (185 and 291 minute). Preoperative prone computed tomography is useful for predicting intractable cases of inguinal hernias. Prone computed tomography can play a significant role in not only typing and differentiating hernias from other diseases, but also in helping surgeons appropriately treat unexpected intractable cases with laparoscopic surgery., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

We treated skin sclerosis with triple therapy consisting of a glucocorticoid, intravenous cyclophosphamide, and double-filtration plasmapheresis. The objective of this study was to analyze its effectiveness in a case series of patients who received triple therapy.We enrolled 8 patients with diffuse cutaneous systemic sclerosis (dcSSc) who received triple therapy at our hospital from 2008 to 2016. We analyzed the mean change in the modified Rodnan skin score (mRSS), percentage of the predicted forced vital capacity (%FVC), percentage of the predicted carbon monoxide diffusing capacity (%DLCO), and serum KL-6 levels from baseline to follow-up.All patients were treated with an intermediate dose of oral prednisolone (30.6 ± 2.1 mg/day) initially. The mean cumulative dose of intravenous cyclophosphamide was 1.4 ± 0.2 g. The mean mRSS decreased significantly at follow-up compared with that at baseline (27.0 ± 3.3 vs 15.8 ± 3.5; P = .03). At the end of the treatment, the mean %FVC and %DLCO were improved moderately, although the differences were not significant. The serum KL-6 levels decreased from 578.9 ± 146.5 to 205.3 ± 43.1 U/ml (P = .02). No significant correlation was found between the change in mRSS or disease duration and the initial skin score severity.Triple therapy may improve skin sclerosis, with effectiveness equal or superior to other reported treatments. This preliminary case series demonstrates the potential of triple therapy for treating dcSSc. However, prospective studies with long-term follow-up should be performed to assess its role.

Background: Recently, we reported that urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), an oxidative stress marker, reflected inflammatory activity in cardiac sarcoidosis (CS). Here, we investigated whether U-8-OHdG levels were associated with ventricular tachycardia (VT) in patients with CS., Methods and Results: This prospective cohort study enrolled 62 consecutive patients with CS, of whom 36 were diagnosed as having active CS based on abnormal 18 F-flurodeoxyglucose accumulation in the heart on positron-emission tomography/computed tomography. The 36 patients with active CS were subdivided as having CS with sustained VT (CS-VT group; n=18) or CS without sustained VT (CS-nVT group; n=18). Twenty-seven patients diagnosed with idiopathic dilated cardiomyopathy served as heart failure controls. U-8-OHdG, brain natriuretic peptide, cardiac function indices, and immunohistological data from subendomyocardial biopsy samples were compared across groups. Immunohistochemical examination of ventricle biopsy samples revealed that the anti-8-OHdG antibody-positive area of cardiac tissue was significantly greater in CS-VT than in CS-nVT or dilated cardiomyopathy and significantly correlated with U-8-OHdG levels (n=58; R =0.61; P <0.00001), which were significantly higher in CS-VT than in CS-nVT (24.6±7.1 versus 15.2±3.8 ng/mg·Cr; P <0.0001). Other baseline characteristics did not differ between the groups. Multivariate analysis indicated that U-8-OHdG was an independent determinant factor for VT. Receiver operating characteristic curve analysis to identify patients with VT resulted in a U-8-OHdG cutoff value of 17.5 ng/mg·Cr (sensitivity, 89%; specificity, 83%; area under the curve, 0.90)., Conclusions: U-8-OHdG levels are associated with VT in patients with active CS diagnosed by 18 F-flurodeoxyglucose positron-emission tomography, providing additive and relevant information about the arrhythmia substrate., (© 2017 American Heart Association, Inc.)

Objective: To establish a methodology for magnetic resonance imaging (MRI) assessment in the diagnosis of cholesteatoma using signal intensity on BLADE diffusion-weighted MRI (BLADE-DWI) and apparent diffusion coefficient (ADC) mapping., Study Design: Retrospective case series., Setting: University hospital., Patients: Participants comprised 29 patients who underwent middle ear surgery and in whom preoperative differential diagnosis between cholesteatoma and other middle ear diseases was difficult using local and computed tomographic findings and required BLADE-DWI., Intervention: Signal intensity ratio (SIR) between the affected region of the middle ear and the pons measured by BLADE-DWI and on ADC maps was evaluated numerically. SIR in an area located near the target lesion in each case was used as a control. Values were compared between both cases in which cholesteatoma was histopathologically confirmed (cholesteatoma group) and cases in which cholesteatoma was excluded on histopathologic examination (noncholesteatoma group)., Main Outcome Measures: Imaging and histopathologic findings., Results: SIR on BLADE-DWI was significantly higher in the cholesteatoma group than in the noncholesteatoma group, although both groups showed significantly higher SIR in the target lesion than in the control area. Moreover, SIR on ADC maps was significantly lower in the cholesteatoma group than in the noncholesteatoma group. The clear cutoff value of SIR on ADC maps was 1.5., Conclusion: The combination of BLADE-DWI and ADC mapping offers a useful imaging tool for accurate detection of middle ear cholesteatoma. Use of SIR can numerically differentiate between cholesteatoma and noncholesteatoma.

Purpose: Intrabullous ventilation in patients with pulmonary emphysema (PE) was cross-sectionally evaluated using dynamic xenon-133 gas single photon emission computed tomography (SPECT)., Methods: Fifty-two patients with PE with a total of 109 bullae of more than 4 cm in maximum diameter underwent xenon-133 gas SPECT. The real xenon-133 gas half-clearance time (T1/2) at each bulla was compared with that at the surrounding lung in the same lobe. The emphysema subtype of the surrounding lung was classified into centrilobular, panlobular, and paraseptal on computed tomography (CT)., Results: All bullae except for one in all patients showed xenon-133 gas wash-in. Of the 108 bullae with wash-in, 95 (87.9%) bullae in 46 (88%) patients showed marked xenon-133 gas retention with a T1/2 beyond 110 s (mean: 184 s ± 91). The surrounding lungs of these bullae also showed marked retention with a T1/2 of greater than 100 s (mean: 174 s ± 82), and the majority (N=92, 96.8%) were centrilobular or panlobular on CT. The remaining 13 (12.0%) bullae in six (11%) patients showed minimal retention with a T1/2 of less than 80 s (mean: 62 s ± 11), regardless of no significant difference in size compared with the bullae with marked retention. All the surrounding lungs of these bullae except for one also showed minimal retention with a T1/2 of less than 70 s (mean: 60 s ± 18), which was significantly less compared with that of the bullae with marked retention (P<0.0001), and the majority (N=11, 84.6%) were paraseptal with or without an interstitially fibrotic change and predominantly located at the lower lung lobe on CT. The T1/2 of the 108 bullae with xenon-133 gas wash-in was significantly correlated with that of the surrounding lungs (r=0.884, P<0.0001)., Conclusion: Intrabullous ventilation in patients with PE appears to depend on the ventilation status of the surrounding lung, and bullae with the surrounding lungs of paraseptal-type emphysema tend to show minimal air trapping. Xenon-133 gas SPECT is useful for assessment of the interaction between intrabullous and surrounding lung's ventilation, which is difficult on CT.

Purpose: Lung perfusion impairment in patients with pulmonary arteriovenous fistula (AVF) was evaluated by automated deep inspiratory breath-hold (DIBrH) perfusion single-photon emission computed tomography (SPECT)-CT fusion images., Methods: Participants were 14 patients with a single (N=6) or multiple nodular AVFs (N=8) diagnosed by contrast-enhanced CT scan and/or pulmonary angiography. After the injection of 185MBq Tc-99m-macroaggregated albumin, a whole-body scan was obtained to quantify an intrapulmonary right-to-left shunt. Subsequently, DIBrH SPECT was obtained using the continuous rotating acquisition mode of a dual-headed SPECT system, which was automatically coregistered with DIBrH CT. The anatomic relationship between AVF and perfusion defects was assessed on the fusion images., Results: The whole-body scan depicted systemic organs indicating the presence of an intrapulmonary right-to-left shunt in all the patients. DIBrH SPECT showed 34 perfusion defects in these patients, which were located at the AVF and in the surrounding lungs of the AVF on the fusion images, regardless of the absence of morphologic abnormality on CT in all the patients. These defects were considered to be caused by the 'steal phenomenon' associated with the high and fast pulmonary arterial flow to each AVF, which were more extensive and severe in the multiple AVFs compared with a single AVF (P=0.0012), occasionally extending to the entire lobe with AVF or even to the adjacent lobe. In five patients, the fusion images detected a total of six tiny AVFs with unexpectedly extensive 'steal phenomenon'-induced defects, which had been missed by other radiological imaging techniques. The summed value of the shunt index estimated by the whole-body scan and the lung perfusion defect extent estimated by DIBrH SPECT was significantly correlated with PaO2 in all the patients (P < 0.0001), with a better correlation compared with the shunt index alone., Conclusion: In addition to the right-to-left shunt, 'steal phenomenon'-induced perfusion defects are common in the surrounding lung of pulmonary nodular AVF and cause hypoxemia. DIBrH SPECT-CT fusion images contribute to the objective evaluation of 'steal phenomenon'-induced lung perfusion impairment in AVF and the detection of tiny, subtle AVFs that may be missed by other radiological imaging techniques.

Purpose: Cross-sectional lung ventilation (V)-perfusion (Q) imbalance in primary pulmonary arterial hypertension (PAH) and passive pulmonary hypertension (PH) was characterized by automated V/Q single-photon emission computed tomography (SPECT)., Materials and Methods: Technegas/macro-aggregated albumin SPECT-derived V/Q SPECT and V/Q profile were automatically built to characterize cross-sectional lung V-Q imbalance in 12 patients with primary (idiopathic or familial) PAH and 15 patients with passive PH associated with left ventricular dysfunction or failure. The abnormality of V/Q distribution in these patients was correlated with PaO2 and pulmonary arterial pressure and with lung morphologic changes on computed tomography (CT)., Results: Markedly low V/Q ratios (reverse V-Q mismatch) in the background lungs with heterogeneous V/Q distribution was seen in 12 of the 12 (100%) patients with primary PAH and in 10 of the 15 (66%) patients with passive PH, which were predominantly seen in the upper lung zone. Including these regions with reverse V-Q mismatch, the V/Q profile frequently showed flattened peaks with asymmetric and broadened V/Q distribution in all patients, with significant correlation between the standard deviation of V/Q ratios in the entire lungs and PaO2 and mean pulmonary arterial pressure (both; P<0.01). At the regions of the lungs with reverse V-Q mismatch, bronchial lumens compressed by dilated pulmonary arteries and heterogeneous lung attenuations were frequently seen on CT., Conclusion: Patients with primary PAH and passive PH seem to characteristically have a high prevalence of reverse V-Q mismatch indicative of an inadequate hypoxic vasoconstriction reflex on V/Q SPECT, frequently accompanied with heterogeneous lung attenuations and compressed airways on CT., (2010 Wolters Kluwer Health / Lippincott Williams & Wilkins.)

Objective: Nonspecific interstitial pneumonia (NSIP) and usual IP (UIP) preferentially involve subpleural lung zones (SPLZ), and may result in characteristic regional lung function impairment. The aim of this study was to characterize cross-sectional lung ventilation (V)-perfusion (Q) imbalance in these disorders on automated V/Q quotient single photon emission computed tomography (SPECT)., Methods: 99mTc-technegas/macroaggregated albumin SPECT-derived V/Q quotient SPECT and V/Q profile were automatically built for assessment of cross-sectional lung V-Q imbalance in 38 patients with NSIP or UIP. The findings of V/Q quotient SPECT were correlated with lung CT morphology. The results were compared with 12 healthy nonsmoker controls and 48 patients with chronic obstructive pulmonary disease., Results: V/Q quotient SPECT showed 81 crescentic SPLZ with high V/Q ratios in 32 patients (84%) with NSIP or UIP, which were not observed in controls and patients with chronic obstructive pulmonary disease. Sixty-three (77.7%) of them were located at high-attenuation areas (reticular and/or ground-glass opacities) with or without small cystic air spaces (honeycombing and/or traction bronchiectasis) on CT, and 12 (14.8%) at normal lung areas. V/Q profile at the lung sections with crescentic SPLZ with high V/Q ratios showed flattened peaks with broadened V/Q ratio distribution compared with controls, and standard deviation of V/Q ratios in the entire lungs was significantly correlated with partial oxygen arterial blood pressure (P = 0.0009) and predicted diffusing capacity of the lungs for carbon monoxide (P = 0.0139). Five of eight patients with NSIP or UIP and with worsening of hypoxemia showed an extension of SPCZ with high V/Q ratios on follow-up V/Q quotient SPECT, without significant changes on CT., Conclusion: A high prevalence of crescentic SPLZ with high V/Q ratios is a characteristic feature of lung V-Q imbalance causing alveolar gas exchange impairment in NSIP and UIP.

Objective: By focusing on a stripe sign (interposed preserved radioactivity between central defects and pleural surface of the lung), the cross-sectional ventilation difference between the central and peripheral lung in pulmonary emphysema was evaluated on Tc-Technegas SPECT, and compared with other forms of chronic obstructive pulmonary disease (COPD)., Methods: Technegas and perfusion SPECT were performed in 47 patients with relatively advanced emphysema, 15 patients with other forms of COPD without alveolar destruction and six controls. The presence or absence of a stripe sign was evaluated at upper, middle and lower lung zones on both SPECT. At stripe sign-positive lung zones on Technegas SPECT in pulmonary emphysema, the pattern of low attenuation areas (LAAs) distribution on X-ray CT was also evaluated., Results: Of the total of 282 lung zones in patients with emphysema, a stripe sign was positive on Technegas SPECT at 153 (54.2%) zones in 27 (57.4%) patients, although less frequently positive on perfusion SPECT at 166 (58.8%) zones in 30 (63.8%) patients. This sign was negative on Technegas SPECT throughout the stripe sign-negative zones on perfusion SPECT. Throughout the lung zones in controls and patients with other forms of COPD, this sign was negative both on Technegas and perfusion SPECT. On X-ray CT, 124 (81%) of 153 stripe-positive lung zones on Technegas SPECT in pulmonary emphysema showed central lung-dominant LAA., Conclusion: In contrast to other forms of COPD, a stripe sign was frequently positive on Technegas SPECT in relatively advanced emphysema, with central-lung dominant LAA on X-ray CT. Relative preservation of peripheral lung ventilation seems to be a characteristic feature of this disease, indicating a lower susceptibility of the peripheral lung for alveolar destruction.

Regional computed tomography attenuation (CTA) alteration at perfusion defects in acute pulmonary thromboembolism (PTE) was comprehensively assessed using deep-inspiratory breath-hold SPECT-CT fusion images. Subjects were 14 acute and 9 chronic PTE patients and 13 control subjects. Regional perfusion, CTA, and intravascular clots were correlated on deep-inspiratory breath-hold SPECT-unenhanced/angiographic CT fusion images. Fusion images visualized hypo-CTA in 57% of the acute PTE patients, which preferentially occurred at extensively and severely decreased perfusion areas caused by central clots. CTA at 35 defects of acute PTE was significantly decreased compared with that of normal lungs (P<0.001), but the degree was less compared with chronic PTE (P<0.0001). Fusion images also revealed variable relationships of clots and regional perfusion/CTA in the distal lungs of each central clot. Fusion images provide important information about the actual effects of intravascular clots on peripheral perfusion/CTA and indicate that lung CTA can be decreased at perfusion defects in acute PTE.

Purpose: To characterize regional ventilation impairment of pulmonary emphysema using dynamic 133Xe single photon emission computed tomography (SPECT) functional images, compared with other forms of chronic obstructive pulmonary disease (COPD)., Methods: Dynamic 133Xe SPECT was performed in 34 patients with emphysema and 15 patients with other forms of COPD. Three-dimensional voxel-based functional images of the half-clearance time (T1/2) mainly reflecting the initial rapid washout of 133Xe gas from the large airways, and of the mean transit time (MTT) reflecting 133Xe gas washout from the entire lungs, including the small airways and alveoli, were created based on an area-over-height method. T1/2 and MTT values were compared with the regional extent of low attenuation areas (%LAA) on density-mask computed tomography images and the diffusing capacity of the lungs for carbon monoxide (DLCO)., Results: The MTT/T1/2 ratio in each lung in emphysema was significantly higher than that in other forms of COPD (1.60+/-0.74 vs. 1.21+/-0.26; P<0.01). In the selected unilateral lungs with similar T1/2 values, MTT values were also significantly higher in emphysema. MTT values in each lung showed a significantly closer correlation with the corresponding %LAA values compared with T1/2 values in emphysema (R=0.698, P<0.0001 vs. R=0.338, P<0.01; P<0.05); while only the T1/2 values showed a significant correlation in other forms of COPD (P<0.0001). In correlation with DLCO, MTT values showed a significantly closer correlation compared with T1/2 values in emphysema (R=0.909, P<0.0001 vs. R=0.555, P<0.001; P<0.05); while either value did not show a significant correlation in other forms of COPD., Conclusion: MTT values are more critically affected in emphysema compared with other forms of COPD without significant alveolar destruction, and MTT and T1/2 values appear to be differently correlated with the regional extent of LAA between these two disorders. Direct comparison of regional T1/2 and MTT values on functional images may contribute to the demarcation of lung pathology of these two disorders.

Purpose: Deep-inspiratory breath-hold (DIBrH) Tc-99m-macroaggregated albumin (MAA) SPECT images were developed to accurately evaluate perfusion impairment in smokers' lungs., Methods: DIBrH SPECT was performed in 28 smokers with or without low attenuation areas (LAA) on CT images, using a triple-headed SPECT system and a laser light respiratory tracking device. DIBrH SPECT images were reconstructed from every 4 degrees projection of five adequate 360 degrees projection data sets with almost the same respiratory dimension at 20 sec DIBrH. Perfusion defect clarity was assessed by the lesion (defect)-to-contralateral normal lung count ratios (L/N ratios). Perfusion inhomogeneity was assessed by the coefficient of variation (CV) values of pixel counts and correlated with the diffusing capacity of the lungs for carbon monoxide/alveolar volume (DLCO/VA) ratios. The results were compared with those on conventional images., Results: Five DIBrH projection data sets with minimal dimension differences of 2.9+/-0.6 mm were obtained in all subjects. DIBrH images enhanced perfusion defects compared with conventional images, with significantly higher L/N ratios (P<0.0001), and detected a total of 109 (26.9%) additional detects (513 vs. 404), with excellent inter-observer agreement (kappa value of 0.816). CV values in the smokers' lungs on DIBrH images were also significantly higher compared with those on conventional images (0.31+/-0.10 vs. 0.19+/-0.06, P<0.0001). CV values in smokers on DIBrH images showed a significantly closer correlation with DLCO/VA ratios compared with conventional images (R = 0.872, P<0.0001 vs. R=0.499, P<0.01)., Conclusion: By reducing adverse effect of respiratory motion, DIBrH SPECT images enhance perfusion defect clarity and inhomogeneity, and provide more accurate assessment of impaired perfusion in smokers' lungs compared with conventional images.

Objective: Three-dimensional multidetector-row computed tomographic lymphography (3D MDCT-LG) with interstitial injection of a widely available nonionic monometric contrast medium iopamidol was used for navigation of breast sentinel lymph node (SLN) biopsy., Methods: 3D MDCT-LG was obtained after massage of the interstitially injection sites of a total of 4-5 mL undiluted iopamidol at periareolar and peritumoral areas in 68 consecutive patients with early-stage breast cancer, using a 4 detector-row CT scanner. Drainage lymphatic patterns and SLN anatomy were assessed on 3D MDCT-LG images. 3D MDCT-LG-navigated SLN biopsy with combined use of blue dye was followed by backup axillary lymph node dissection to evaluate accuracy of SLN biopsy., Results: The 3D MDCT-LG images clearly localized primary SLNs by visualizing the direct connection between these nodes and their afferent lymphatic vessels on detailed anatomy of the surrounding structures in all patients. Drainage lymphatic pathways on these images were classified into 4 patterns: single route/single SLN (39 cases, 57%), multiple routes/multiple SLNs (10 cases, 15%), single route/multiple SLNs (9 cases, 13%), and multiple routes/single SLN (10 cases, 15%). Under 3D MDCT-LG navigation, SLNs was found at the accurate location in all patients. With backup axillary lymph node dissection, metastasis was found in 14 (20%) patients, and 8 of these patients had metastasis only in the preoperatively identified SLNs. In other 5 positive patients, metastasis was found both in the SLN and non-SLNs. However, micrometastasis eventually was found only in non-SLN in an elderly patient. Overall, the sensitivity, false-negative rate, and accuracy of 3D CT-L-navigated SLN biopsy were 92% (13/14 patients), 7% (1/14 patients), and 98% (67/68 patients), respectively., Conclusions: Topographic 3D interstitial MDCT-LG can be a widely available and reliable navigator for breast SLN biopsy.

Purpose: Preferential location of acute pulmonary thromboembolism (PTE) induced consolidative opacities (infarction/atelectasis) was determined on respiratory gated perfusion SPECT-CT fusion images., Method: Gated end-inspiratory perfusion SPECT images were obtained in 21 patients with acute PTE and 17 patients with inflammatory diseases, using a triple-headed SPECT system and a respiratory tracking device. Anatomical relationships of consolidative opacities and perfusion defects were assessed on gated SPECT-rest inspiratory CT fusion images. The size and radioactivity of perfusion defects with acute PTE consolidative opacities were compared with those of defects without these opacities. The contribution of fusion images for differential diagnosis of acute PTE induced and inflammatory disease induced lesions was evaluated by receiver operating characteristic (ROC) curve analysis., Results: Of the total 56 acute PTE induced consolidative opacities, 42 (75%) were located at the peripheral interface between the severely decreased and adjacent relatively preserved perfusion areas within wedge shaped perfusion defects on fusion images. These defects with consolidative opacities were significantly larger and had taken up less radioactivity compared with those in the 86 defects without these lesions (P<0.0001). In contrast, of the 29 inflammatory disease induced opacities, 14 (48.2%) had the matched defects and 13 (44.8%) were located at the proximal portion of defects. These preferential locations of acute PTE induced and inflammation induced lesions were significantly different (P<0.01). In ROC curves, the combined reading of fusion images showed a significantly higher differential diagnostic accuracy compared with the reading of CT and SPECT images alone (P<0.01)., Conclusions: Acute PTE induced consolidative opacities preferentially occur at the peripheral lung interface between severely decreased and adjacent relatively preserved perfusion areas within relatively large and severely decreased perfusion defects. The fusion images, which provide an accurate assessment of the morphological-perfusion defect relationship could, potentially, provide a differential diagnosis between acute PTE induced and inflammatory disease induced lesions.

Aim: Respiratory-gated thallium-201 chloride (201Tl) single photon emission computed tomography (SPECT) was used in preliminary investigations to reduce the adverse respiratory motion effects observed on standard ungated SPECT images and to obtain reliable fusion images with computed tomography (CT) in patients with malignant lung tumours., Methods: Fifteen patients with primary lung cancer (n=10) or metastatic lung tumours (n=5) underwent gated SPECT 20 min after intravenous injection of 148 MBq 201Tl, using triple-headed SPECT and laser light respiratory tracking units. Projection data were acquired by a step and shoot mode, with 20 stops over 120 degrees for each detector and a preset time of 30 s for each 6 degrees stop. Gated end-inspiratory and ungated images were obtained from 1/8 data centred at peak inspiration for each regular respiratory cycle and for the full respiratory cycle data, respectively. The degree and size of tumour 201Tl uptake were compared between these images by regions of interest (ROI) analysis. Gated SPECT images were registered with rest inspiratory CT images using an automated three-dimensional (3D) image registration tool. Registration mismatch was assessed by measuring the 3D distance of the centroid of 14 201Tl-avid peripheral tumours. Attenuation correction of gated SPECT images was performed using CT attenuation values of these fusion images., Results: Gated SPECT images improved image clarity and contrast of tumour 201Tl uptakes compared with ungated images, regardless of the decreased count density due to the use of gated images. The lesion-to-normal (L/N) lung count ratios and ROI size in 18 well-circumscribed 201Tl-avid tumours were significantly higher and smaller on gated images (both P<0.0001). Gated images showed positive 201Tl uptakes in two small peripheral tumours, although negative on ungated images, and demarcated 201Tl-avid tumours from adjacent 201Tl-avid lymph node or surrounding focal 201Tl uptakes caused by other pathology, although these were not clearly demarcated on ungated images. On fusion images, gated images yielded a significantly better SPECT-CT matching compared with ungated images (P<0.0001). Fusion images accurately localized 201Tl uptakes of tumour/lymph node and other focal pathological/physiological conditions. Attenuation-corrected gated SPECT images further facilitated the detection of 201Tl uptake in small or deeply located lesions, with significantly increased L/N ratios., Conclusion: Gated SPECT images facilitate the detection of tumour 201Tl uptake and provide reliable SPECT-CT fusion images, which contribute to accurate interpretation and attenuation correction of Tl SPECT images.

Purpose: Experimental and clinical evaluation of the potential utility of indirect computed tomographic lymphography (CT-LG) with intrapulmonary injection of iopamidol for preoperative localization of sentinel lymph node station in non-small cell lung cancer., Methods: CT-LG with intrapulmonary injection of 0.5 mL of undiluted iopamidol was performed in 10 dogs using a multidetector-row CT unit, followed by postmortem examination of enhanced lymph nodes in 5 of these dogs. The CT-LG with peritumoral injection of 1 mL of the contrast agent was also performed in 9 patients with non-small cell lung cancer without lymphadenopathy. At surgery, enhanced lymph nodes were resected under CT-LG guide, followed by standard lymph node dissection with macroscopic and histologic examination. A significant enhancement of lymph nodes was determined when CT attenuation value was increased with 30 Hounsfield units (HU) compared with precontrast images., Results: CT-LG visualized a total of 15 enhanced lymph nodes (on average, 1.5 nodes per animal) within 2 minutes after contrast injection in the 10 dogs, with average size of 6.7+/- 1.9 mm and average maximum CT attenuation of 149 +/- 41 HU. All the 8 enhanced nodes in 5 dogs were found in the appropriate anatomic locations in postmortem examinations. Without noticeable complications, CT-LG visualized 30 ipsilateral intrathoracic lymph nodes including 19 hilar/pulmonary and 11 mediastinal nodes in the 9 patients (on average, 2.2 hilar/pulmonary and 1.1 mediastinal nodes per patient) within 2 minutes after contrast injection, with average size of 4.7+/- 0.4 mm and average maximum CT attenuation of 134 +/- 52 HU. At surgery, all these enhanced nodes could be accurately found and resected under CT-LG guidance. Metastasis was not evident in either of these enhanced lymph nodes or the remaining distant nodes in all patients., Conclusion: Quick and accurate localization of sentinel lymph node station on detailed underlying lung anatomy by using indirect CT-LG may be of value to guide selective lymph node dissection for minimally invasive surgery in non-small cell lung cancer.

Purpose: Respiratory gated perfusion single photon emission computed tomography (SPECT) was applied to reduce respiratory lung motion effects and to reliably assess perfusion impairment in various lung diseases., Methods: After injection of 259 MBq of 99mTc macroaggretated albumin (99mTc-MAA), gating was performed using a triple-headed SPECT unit connected to a physiological synchronizer in a total of 35 patients with either obstructive lung diseases (n = 14), pulmonary embolism (n = 8), small lung nodules (n = 7) or acute interstitial pneumonia (n = 6). Projection data were acquired in a 64 x 64 matrix, with 20 stops over 120 degrees for each detector with a preset time of 15 s for each stop. Inadequate data for the respiratory cycle were automatically eliminated. In addition to end inspiration images and end expiration images derived from 12.5% threshold data centred at peak inspiration and expiration for each respiratory cycle, respectively, an ungated image was obtained from full respiratory cycle data., Results: Gated images were completed for 13.7 +/- 1.8 min in all subjects. Although the total lung radioactivity of the gated images were reduced to approximately 13% of that of the ungated images, these gated images showed uniform perfusion in the unaffected lungs and visualized a total of 94 (21.9%) additional perfusion defects against 429 defects visualized on ungated images in 31 patients with focal perfusion defects. Among the perfusion defects visualized on both gated images, the defect size was occasionally larger on the end inspiration images. The end expiration images showed significantly higher lesion-to-normal lung radioactivity ratios compared with those on the end expiration and ungated images in the affected lower lungs throughout the lung diseases. Radioactivity changes per pixel between end inspiration and end expiration images in the affected lower lungs of the obstructive lung diseases were significantly lower compared with those of pulmonary embolism and acute interstitial pneumonia (P<0.0001 and P<0.01, respectively)., Conclusion: This technique appears to enhance the clarity of perfusion defects, and lung radioactivity changes between end inspiration and end expiration may characterize regionally impaired ventilation status.

Purpose: To evaluate a new approach of magnetic resonance (MR) lymphography with intraalveolar injection of a conventional extracellular contrast agent (gadopentetate dimeglumine) for imaging lymphatic basin draining from specific portions of the lung., Methods: Three-dimensional T1-weighted spoiled gradient-recalled echo MR sequence images were acquired serially before and for 40 minutes after intraalveolar injection of gadopentetate dimeglumine in a total of 14 anesthetized beagle dogs. Six of these dogs received 1 mL undiluted and low-concentration (75%) contrast agent into the same portion of the right caudal lobe during a 7-day interval. In all dogs, including these 6 dogs, MR lymphography was repeated with injection of the low-concentration contrast agent into different lung regions at 7-day intervals to evaluate the differences of the visualized draining lymphatic station. Lymphatic enhancement was quantified by percent increases of signal intensity against precontrast. Postmortem examination of the lymphatic anatomy was performed in 7 of these animals., Results: In all dogs, the lymphatic station draining from the injection sites was visualized within 5 minutes after contrast injection. The maximum percent increase of signal intensity of the same middle tracheobronchial lymph nodes was significantly greater with a low-concentration (75%) contrast agent than with an undiluted one in the same 6 dogs (n = 6, 247.6 +/- 30.5% vs. 204.2 +/- 33.8%; P < 0.01). Different lymphatic stations draining from the different injection sites were visualized in all dogs. In a total of 12 MR studies that showed extended nodal enhancement after injection of the low-concentration contrast agent, the enhancement peak of the most proximal nodes (n = 12) from the injection sites appeared earlier than that of their distant nodes (n = 12), with a maximum percent increase of signal intensity of 249.8 +/- 42.4%. The visualized lymph nodes were found in the appropriate locations postmortem, with significant correlation for nodal sizes (r = 0.965; P < 0.0001)., Conclusion: MR lymphography with low-concentration gadopentetate dimeglumine can quickly and sufficiently visualize the drainage lymphatic station from specific lung portions, and may have the potential of sentinel node mapping in lung cancer.

Purpose: The capability of the interstitial magnetic resonance lymphography (MR-LG) using a widely available extracellular contrast agent, gadopentetate dimeglumine, for the visualization of normal and interrupted lymphatic drainage was tested in dog legs., Materials and Methods: With a 7-day interval, 1 mL and 2 mL undiluted gadopentetate dimeglumine were injected intradermally into the dorsal foot of both hind legs of 12 dogs. T1-weighted 3-dimensional (3D) spoiled gradient-echo (repetition time/echo time = 6.7/1.6 ms) and maximum intensity projection (MIP) images covering the legs and pelvic region were acquired at 1.5 T for 10 minutes after 30 seconds gentle massage at the injection sites. These dogs also underwent the MR-LG with 2 mL of this contrast agent 7 days after surgical ligation of the popliteal lymphatic vessels., Results: In the normal dogs, the interstitial MR-LG quickly and consistently visualized the direct connection of the lymphatic vessels and lymph nodes draining from the injection sites up to the inguinal region, without any late adverse effects. The enhancement effect was significantly greater with a 2-mL dose than with a 1-mL dose. After lymphatic obstruction, the MR-LG clearly revealed the anatomic compromises of the lymphatics, such as poor enhancement of the affected lymphatic vessels and lymph nodes, collateral lymphatic vessels, abnormal soft-tissue enhancement, and delayed lymphatic migration of the contrast agent. The topographic 3D images provided a comprehensive anatomy of these normal and compromised lymphatic drainage., Conclusion: Although gadopentetate dimeglumine is not lymphotropic, the interstitial MR-LG using this T1-contrast agent appears to have potential for quick and sufficient mapping of the lymphatic drainage from the injection sites and for the characterization of interrupted lymph flow.

Rationale and Objectives: The capability of an indirect computed tomographic lymphography (CT-LG) using a nonionic monometric contrast medium iopamidol for visualizing breast lymphatic pathways was preliminarily tested., Materials and Methods: In 10 female dogs, a total of 0.5 and 1 mL of undiluted iopamidol was injected subcutaneously into the skin areas overlying the both caudal mammary glands. Contiguous 2-mm-thick multidetector raw helical CT images were obtained through the upper thorax and axilla before and during 60 minutes after gentle massage at the injection sites, with reconstruction into three-dimensional (3D) postcontrast CT images. The first lymph node (1st LN) directly draining from the injection sites was marked under CT guidance, followed by pre- and postmortem examinations. This CT-LG with 2-mL iopamidol was also attempted in five human female volunteers., Results: Even with 0.5-mL iopamidol, the CT-LG clearly visualized the direct connection of the 1st LN and lymphatic vessels draining from the injection sites throughout the examination time in all the animals, with the maximum CT attenuation of 269 Hounsfield units (HU) +/- 137 in the 1st LN on the first postcontrast images. The topographic 3D images provided comprehensive anatomic outlines of these lymphatic pathways. Of the total of 20 opacified 1st LN and 110 distant nodes, all the 1st LN (100%) and 92 (83.6%) distant nodes could be resected at pre- or postmortem, with a good correlation with the CT images. The CT-LG also effectively localized the 1st LN with the maximum attenuation of 223 HU +/- 63 in the human volunteers, without any significant late adverse effects., Conclusion: Indirect CT-LG with iopamidol may have excellent potential for visualizing breast lymphatic drainage and for preoperative localization of breast sentinel lymph nodes.

Rationale and Objectives: The potential of a noncontrast, electrocardiography (ECG)-gated fast-spin-echo (FSE) MR imaging (MRI) to monitor dynamically altered regional lung perfusion was assessed in acute and temporal pulmonary embolic and airway obstruction dog models., Materials and Methods: After acquisition of ECG-gated multiphase FSE MR images during one cardiac cycle, the two phase images of the minimal lung signal intensity (SI) during systole and the maximal SI during diastole were acquired in the lower lung levels in six normal dogs, in 13 dogs before and for 35 minutes after temporal microvascular embolization in regional lungs with gradually degradable starch microspheres of spherex, and in 12 dogs before and for 45 minutes after bronchial occlusion with a balloon catheter. In three of the 13 embolic models, the opposite lung areas, however, were permanently embolized with enbucrilate. Subtraction between the diastolic and systolic images yielded a perfusion-weighted image. The results were compared with a gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced dynamic perfusion MRI, which was subsequently performed after the ECG-gated MRI in each animal., Results: The multiphase FSE images provided cardiac-dependent pulsatile lung SI changes, and the subtracted perfusion-weighted images provided a uniform perfusion map in normal lungs. In all the embolic models, the subtracted perfusion-weighted images showed gradual disappearance of the spherex-induced perfusion deficits, while the enbucrilate-induced perfusion deficits persistently remained in the three animals. In all airway obstruction models, these images showed gradually decreased perfusion in the hypoventilated areas. These results were consistent with the matched Gd-DTPA-enhanced pulmonary arterial perfusion phase images in each animal., Conclusion: This noncontrast perfusion MRI may have excellent potential for continuously monitoring dynamically changed regional lung perfusion within a short time on its high spatial resolution cross-sectional images.

Rationale and Objectives: A contrast-enhanced dynamic magnetic resonance (MR) study was performed experimentally and clinically to describe perfusion characteristics of radiation-injured lung according to pathologic phases., Methods: The MR study was performed before and at 0.5, 1, 2, 3, 4, and 7 months after 40 Gy-dose irradiation to the right hemithorax in 8 dogs, and clinically in 12 lung lesions of 9 patients with acute or fibrotic radiation pneumonitis. Altered Gd-DTPA kinetics in the affected lungs was assessed by time-signal intensity curves. MR findings were correlated with lung histology and CT images., Results: Within 1 month after irradiation, the irradiated animal lungs showed focal and persistent contrast enhancement relative to nonirradiated lungs. This abnormality was pronounced during the next 2 months. After 4 months, irradiated lungs conversely showed lower enhancement during the Gd-DTPA first-pass but were followed by persistently greater enhancement during Gd-DTPA redistribution phase. Similar differences in enhancement abnormalities between acute and fibrotic radiation pneumonitis were clinically observed., Conclusion: These findings indicate that Gd-DTPA kinetics can be altered according to the histopathologic change in early/acute radiation pneumonitis and radiation fibrosis and that the contrast-enhanced perfusion MRI may help differentiate the phases of radiation pneumonitis.

Rationale and Objectives: Gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-based aerosol ventilation and perfusion magnetic resonance (MR) images were used to define regional functional impairment in acute airway obstruction (AO) and pulmonary embolic (PE) dog models., Methods: The aerosol study was performed in 10 anesthetized normal dogs in a supine position during 20-minute spontaneous inhalation of an aerosol of 100- or 200-mmol-Gd/L Gd-DTPA solute produced by an ultrasonic nebulizer in an open-circuit delivery system, combined with a dynamic perfusion study after a 3-second intravenous bolus injection of a 0.1 mmol/kg dose of Gd-DTPA. These MR studies were also performed in the same 10 dogs approximately 30 minutes after obstructing the segmental (n = 6) or lobar (n = 4) bronchus with a balloon catheter, and in another six dogs after segmental (n = 6) and lobar (n = 4) pulmonary arterial embolization with enbucrilate. Regional lung enhancement was assessed on time-signal intensity (SI)-curves and ventilation- and perfusion-weighted images produced by a subtraction technique., Results: The normal lungs were gradually and gravity-dependently enhanced with time after Gd-DTPA aerosol inhalation regardless of the respiratory SI changes, except for three animals with the fastest breathing rate. The averaged maximal relative lung SI increase against the baseline in the successful animals was significantly greater in the slowly and deeply breathing animals than in the fast and shallow breathing animals, regardless of the difference in Gd-concentration (100 mmol Gd/L: 153.3% +/- 69.7% vs. 54.2% +/- 23%; P < 0.001; and 200 mmol Gd/L: 189.7% +/- 68.0% vs. 75.6% +/- 42.2%; P < 0.0001, respectively). There was an additional enhancement of 382% +/- 101 in the ventral lung and 722% +/- 160 in the dorsal lung on the pulmonary arterial phase perfusion image even in the slowly and deeply breathing animals who inhaled 200-mmol-Gd/L aerosol, and the enhancement effect was significantly greater compared with that with the aerosol (P < 0.0001). The ventilation- and perfusion-weighted images clearly defined the regionally matched perfusion-ventilation deficits in all the AO models, and the regionally mismatched perfusion-ventilation in all the PE models., Conclusion: Gd-based aerosol can provide efficient lung enhancement in spontaneously and adequately breathing animals, using a relatively noninvasive aerosol delivery system. The combined use of Gd-based perfusion MR imaging may be acceptable for defining regionally impaired function associated with acute AO and PE.

Rationale and Objectives: To assess the alteration in renal transit of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) in dog kidneys after acute vascular occlusion on dynamic echo-planar imaging (EPI)., Methods: Dynamic 240-ms EPI series (repetition time/echo time/inversion time [TR/TE/TI] = 3000/42.1/100 ms) of the midcoronal plane of both kidneys of dogs anesthetized by intravenous administration of phenobarbital sodium and ketamine hydrochloride were obtained before and after ligation of the left renal vein (n = 6) or artery (n = 6) for 40 minutes after a 2-second-rate bolus injection of a 0.05 mmol/kg dose of Gd-DTPA. Renal Gd-DTPA transit was analyzed on the time-DeltaR2* curves in each layer of the outer cortex (OC), juxtamedullary cortex and outer zone of the medulla (JMC-OM), and the inner zone of the medulla (IM). The results were compared with those in six normal animals and those of a fast gradient-echo T1-weighted dynamic study performed in other vein- (n = 6) or artery- (n = 6) occluded animals and six normal animals. The histopathological basis of the altered Gd-DTPA transit was also evaluated., Results: The dynamic EPI showed rapid Gd-DTPA transit through each of the five concentric layers, with three separate peaks on the time-DeltaR2* curves. The vein-occluded kidneys showed immediate swelling, with a significant increase in the cross-sectional area proportion of the JMC-OM layer compared with normals (32% +/- 2% vs 24% +/- 2%, P < 0.0001) and intensely congested capillaries, tubular, obliterated material, and gradual and persistent enhancement of the OC and JMC-OM layers but poor Gd-DTPA migration to the IM layer. The artery-occluded kidneys showed a significant reduction in the entire cross-sectional area compared with normals (1352 +/- 69 vs 1432 +/- 47 mm(2), P < 0.05) and poor enhancement, with significant decreases in the area under the time-DeltaR2* curve of the OC and JMC-OM layers compared with the vein-occluded kidneys (79 +/- 50 vs 324 +/- 108 and 82 +/- 42 vs 326 +/- 113, respectively; both P < 0.0001), despite minimal histological damage. In both models, the nonaffected kidneys showed significant increases in the area under the time-DeltaR2* curves compared with baseline. The time course of vascular and tubular Gd-DTPA transit was more detailed by the EPI study than by the T1-weighted imaging study., Conclusions: Echo-planar imaging has an excellent ability to follow the rapid, renal Gd-DTPA transit through the regional anatomy of the canine kidney. After venous occlusion, the JMC-OM layer may be the most affected site, primarily causing renal swelling and interruption of tubular Gd-DTPA transit and concentration. In contrast, an initial block of vascular Gd-DTPA inflow is the primary effect of arterial occlusion. Nonaffected kidneys seem to compensate by increasing excretion of Gd-DTPA.

Rationale and Objectives: We conducted an animal study to describe and interpret the perfusion characteristics of oleic acid (OA)-injured lungs on gadopentetate dimeglumine (Gd-DTPA)-enhanced dynamic perfusion magnetic resonance (MR) imaging., Methods: Fourteen dogs received an intravenous OA infusion in the supine (n = 4), prone (n = 4), and right lateral decubitus (n = 6) positions, and 10 minutes later these animals in the same postures underwent the dynamic MR study. Regional Gd-DTPA kinetics was analyzed by the time-signal intensity (SI) curves and by qualitative functional map images of the mean transit time that was representative of the mean circulation time in the vascular bed and the average cumulative sum of the relative increases in SI representative of Gd-DTPA distribution volume during Gd-DTPA first pass. The results were compared with those in six control animals and in another six animals that underwent the MR study 3 minutes (n = 3) and 60 minutes (n = 3) after OA infusion. The MR findings were correlated with the distribution of lung damage and the infused OA particles as assessed by histology., Results: The dynamic MR study showed postural shifts on the gravity-dependent perfusion map of normal lungs. Contrast enhancement during Gd-DTPA first pass in the lung was lower and more heterogeneous in the OA-injured lung models than in controls but was followed by conversely greater and persistent enhancement during the Gd-DTPA redistribution phase. Regardless of the postures for OA infusion, these abnormalities were predominant in the dependent lungs and became more pronounced with time after OA infusion, where more prominent capillary obstruction with OA droplets and alveolar/interstitial edema were histologically observed. On the functional map images, greater mean transit time and the average cumulative sum of the relative increases in SI values were also predominantly distributed in the dependent lungs., Conclusions: Low and heterogeneous enhancement was observed during Gd-DTPA first pass but was followed by persistent enhancement during the Gd-DTPA redistribution phase, and predominant abnormalities in the dependent lungs may be characteristic features of the perfusion of OA-injured lungs. The histological correlations indicate that these abnormalities may reflect OA-induced pathophysiologies associated with capillary OA obstruction, increased vascular resistance, and capillary permeability/extravascular spaces and that lung damage may be gravity dependent.

Unlabelled: 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.

We report on six patients with chronic pulmonary embolism who underwent 123I-IMP and 99Tcm-MAA lung SPET before and after thromboendarterectomy. 123I-IMP lung SPET can assess the viability of lung parenchyma, because it is a non-particulate agent that accumulates in the endothelial membranes of pulmonary capillaries. Chronic pulmonary thromboembolism accompanied by pulmonary hypertension has a poor prognosis that may be improved only by thromboendarterectomy. We compared 123I-IMP and 99Tcm-MAA lung SPET in terms of functional improvement after such surgery. After thromboendarterectomy, all six patients were functionally improved, according to the criteria of the New York Heart Association. The pre- and post-surgery percentage of vascular obstruction did not differ significantly with 99Tcm-MAA lung SPET (44.8 +/- 11.2% and 32.5 +/- 15.6% pre- and post-surgery, respectively). In contrast, 123I-IMP lung SPET revealed a significant pre- versus post-surgery difference (15.5 +/- 9.5% and 3.3 +/- 5.9% pre- and post-surgery, respectively). 123I-IMP lung SPET could be useful for evaluating thromboendarterectomy because pulmonary parenchymal viability owing to arterial microvasculature can be estimated.

Preliminary studies were carried out of regional ventilation in lung cancer using three-dimensional (3D) display of dynamic pulmonary 133Xe single photon emission tomography (SPET). Transaxial equilibrium and washout images were obtained from SPET data acquired with an acquisition time of 30 s using a triple-detector SPET system in 39 patients with lung cancer. After reconstructing colour-illuminated, surface-rendered 3D images of equilibrium and 3-min washout (WO3), a single 3D fusion display was created from these two different time-course image sets, in which the 3D WO3 image indicating 133Xe retention was visible through the 3D equilibrium image delineating lung contours. The extent of retention was assessed using the 133Xe retention index, defined as the ratio of summed pixels of the segmented WO3 data to those of the segmented equilibrium data. 133Xe SPET was highly sensitive and specific for the presence of regional ventilation abnormalities associated with endobronchial tumour or bronchial compression due to enlarged lymph nodes. These abnormalities were demonstrated irrespective of the presence or absence of secondary changes distal to the tumour on the chest computed tomography scan. The geometrically realistic 3D fusion display enhanced anatomic localization of the regional ventilation abnormalities compared to the information from multislice tomograms, and the 133Xe retention index correlated well with %FEV1 (r = 0.828). This topographic 3D display for 133Xe SPET allows better perception of anatomic localization and extent of 133Xe retention. It will be useful for assessing regional ventilatory function in patients with lung cancer.

The level of Na(+)-K+ adenosine triphosphatase (ATPase) has been demonstrated to be correlated with tumour growth potential, and accelerated active transport of K+ carried out by Na(+)-K+ ATPase is said to be a trigger of 201Tl affinity for malignant tumour cells. Therefore, 201Tl scintigraphy appears to be a good indicator for evaluation of changes of tumour proliferative potential after treatment. In the present study, the usefulness of 201Tl scintigraphy for monitoring radiotherapeutic effects was evaluated in VX-2 tumours irradiated with variable doses (10-40 Gy of radiation). Changes in 201Tl uptake were compared with tumour growth, and 201Tl uptake on day 7 after irradiation was compared with tumour bromodeoxyuridine (BrdU) uptake, which reflects DNA synthesis. All the treated tumours showed dose-dependent diminished 201Tl uptake, accompanied by either dose-dependent tumour growth delay or tumour regression/resolution. The diminished 201Tl uptake had already appeared on day 7 after irradiation, accompanied by diminished BrdU uptake, although, at this time, the tumour volumes were increased, or were not significantly decreased compared to pre-irradiation. Moreover, the 20 Gy tumours demonstrated two different tumour growth patterns, each accompanied by a different degree of reduction of 201Tl uptake. These findings suggest that the degree of reduction of tumour 201Tl uptake following irradiation can reflect the degree of suppressed proliferative activity in the treated tumours, and that assessment of altered 201Tl uptake at a relatively early time following irradiation allows prediction of subsequent tumour growth, regardless of the tumour volume.

The difference in 201Tl-chloride (201Tl) accumulation on single photon emission computed tomography (SPECT) between 58 benign (58 cases) and 48 malignant (46 cases) thoracic lesions, each of more than 20 mm in diameter was investigated. In the 34 benign and 48 malignant lesions depicted in both early (15 min) and delayed (3 h) images there was no significant difference in the mean early and delayed uptake ratios of lesion to normal contralateral lung between benign and malignant. However, the retention index in the lesion derived from (delayed ratio--early ratio)/(early ratio) x 100% showed a significant difference (benign -4.30 +/- 13.6% versus malignant 23.3 +/- 18.9%, P < 0.01), indicating the poor 201Tl retention in the benign lesions. Using the criteria of nondepiction in the delayed image or a negative retention index, 81.1% accuracy and 95.2% predictive value for diagnosis of benign lesions were obtained. Thus, 201Tl SPECT appears to have potential usefulness in the diagnosis of benign thoracic lesions.

99Tcm-diethylene triaminepenta-acetic acid (99Tcm-DTPA) lung scintigrams were investigated in 11 patients with radiation pneumonitis to assess the alteration of clearance of this small solute. Thirty minutes after the injection of 99Tcm-DTPA, all 11 patients showed abnormal accumulation. This uptake was seen in the areas with reduced 99Tcm-macroaggregated albumin activity. The curves of the lung/heart ratios obtained after 1 min after injection of 99Tcm-DTPA in areas showing abnormal accumulation were of three types. Comparison of the slope for the initial 5 min of the lung/heart curves between the abnormal accumulation sites and the contralateral non-irradiated lung revealed a significant difference. The uptake ratio (the mean counts of the last frame divided by initial peak count) was related to the degree of abnormal accumulation in the radiation pneumonitis. Moreover, study of rabbits with radiation pneumonitis revealed similar behaviour by 99Tcm-DTPA as observed clinically. This simple and rapid method may be useful in detecting and monitoring the altered regional kinetics of 99Tcm-DTPA in radiation pneumonitis.

Radiation-induced alteration of intrapulmonary kinetics of 123I-IMP was investigated in 11 rabbits receiving a 50 Gy dose of radiation to one lung. In all 13 examinations of these rabbits, 3-17 weeks following radiation, the delayed images of 123I-IMP lung scintigrams showed abnormal accumulation in the irradiated lungs. The time-activity curves of the irradiated lung following injection of 123I-IMP had shallower downslopes of both the initial fast phase and the following slow phase than those of the non-irradiated lung. Finally the radioactivity of the irradiated lung exceeded that of the normal lung. The altered intrapulmonary kinetics of 123I-IMP in the irradiated lung was clearly confirmed. 99Tcm-MAA lung perfusion scintigrams showed reduced uptake in the irradiated lungs; the uptake decreased with time following radiation. Pulmonary arterial perfusion was considered to influence the distribution and kinetics of 123I-IMP, however, those of 123I-IMP did not reflect only the pulmonary arterial perfusion observed by 99Tcm-MAA scintigrams. Chest radiography and histological studies revealed a relatively slight change or injury of the irradiated lung in these rabbits. These results indicate that this agent could be useful in detecting and assessing early lung injury induced by radiation, and will give us pathological information in addition to lung perfusion in the peripheral area where the large 99Tcm-MAA molecule cannot reach.

To investigate the intrapulmonary kinetics of N-isopropyl-p-I-123-iodoamphetamine (123I-IMP), lung scanning with 123I-IMP was performed in patients with various lung disorders. Compared with the normal lung field, abnormal accumulation of 123I-IMP was detected in all patients in delayed imaging performed 24 h after 123I-IMP injection. These sites were within areas of absent or reduced perfusion observed by pulmonary perfusion scanning using 99Tcm-macroaggregated albumin (99Tcm-MAA). A similar phenomenon was seen in additional experiments in rabbits with regional pulmonary arterial hypoperfusion resulting from a balloon catheter-induced bronchial occlusion. 123I-IMP accumulation in areas where 99Tcm-MAA images are absent or decreased may be explained by the ability of 123I-IMP to penetrate significantly narrowed microvascular beds with reduced perfusion. Our clinical and experimental results indicate that pulmonary arterial perfusion, particularly hypoperfusion, influence the pulmonary kinetics of 123I-IMP. This compound is a potentially useful non-particulate agent for the assessment of pulmonary arterial perfusion.

Tumour scintigraphy using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) was investigated in VX-2 tumours implanted in the muscles of the lower legs of rabbits to assess the feasibility of using this agent clinically for this procedure. On the time-activity curves for 99Tcm-HMPAO in the tumour, an initial peak and a subsequent decrease of radioactivity immediately after the initial peak were observed, while there was a slow, gradual decrease of activity over the next hour. The tumour/normal muscle ratio of HMPAO activity during this period was high and constant, and was independent of time. Comparison of the static images of 99Tcm-HMPAO with angiography and histological findings suggests that the tumour image of 99Tcm-HMPAO reflects tumour blood perfusion. These findings indicate that the distribution of 99Tcm-HMPAO on static images can provide a qualitative assessment of the perfusion of the tumour, despite the limitations of this tracer for quantifying tumour blood flow due to its early efflux from the tumour.

The role of the calcium ion in central cardiovascular regulation was investigated by injecting a calcium channel blocker, diltiazem, intracerebroventricularly (i.c.v.) in urethane-anaesthetized, DOCA-salt hypertensive rats. This produced a fall in blood pressure and bradycardia with corresponding decreases in abdominal sympathetic nerve activity. However, a similar amount of diltiazem injected intravenously (i.v.) did not affect abdominal sympathetic nerve activity despite an accompanying vasodepression. The responses to i.v. injections of diltiazem were not different between the two groups; however, the magnitude of the blood pressure fall, bradycardia and sympathetic inhibition with i.c.v. injections was greater in the DOCA rats than in the sham-operated animals. These results suggest that diltiazem causes the central nervous system to decrease the sympathetic nerve outflow. The augmented central vasodepressor responses to diltiazem in DOCA-salt hypertensive rats may indicate that calcium metabolism in the central nervous system is disrupted and that this is of importance in the pathogenesis of DOCA-salt hypertension in rats.

The origin of an endogenous digitalis-like substance in rats was investigated. The tissue content of the substance measured by radio-immunoassay was highest in the pituitary gland, with a decreasing gradient through the hypothalamus, forebrain, cerebellum, brain stem, heart, liver and kidney. Sodium loading decreased the content in the hypothalamus and increased the urinary excretion of the substance. The urinary output of the substance decreased after electrical lesions of the anteroventral third ventricle in the brain. The content increased in the hypothalamus and decreased in the plasma when the axonal flow of neurosecretion was interrupted with intracerebroventricular injections of colchicine. These results suggest that the digitalis-like substance could be produced in the hypothalamus and secreted from the pituitary gland like vasopressin, and that sodium loading increases the turnover of the substance in the hypothalamus.

We studied the role of the adrenals on the plasma levels and urinary output of the digoxin-like immunoreactivity in order to elucidate the interrelationship between the adrenals and hypothalamic digoxin-like immunoreactivity. Urine was collected for 24 h 6 days after the bilateral adrenalectomy and then rats were killed by decapitation. Urinary excretion of digoxin-like immunoreactivity did not differ significantly between the sham-operated and adrenalectomized groups, regardless of sodium intake. Plasma levels did not change significantly with sodium-loading, and adrenalectomy did not significantly affect the plasma concentrations of the immunoreactivity. However, bilateral adrenalectomy increased the content of digoxin-like immunoreactivity in the hypothalamus significantly in both rat groups fed with a regular (P less than 0.05) and a high-salt (P less than 0.02) diet. However, when the levels were measured only 16 h after bilateral adrenalectomy, both plasma and hypothalamic contents were significantly higher in the high-salt than the regular-salt group. The correlation between the plasma and hypothalamic content was significant (P less than 0.01). These results strongly suggest that digoxin-like immunoreactivity is produced in the hypothalamus but not in the adrenals, and that the adrenal glands influence the turnover of the hypothalamic endogenous digitalis-like substance.