Regional pulmonary blood flow during acute pulmonary edema: a PET study

We used positron emission tomography to evaluate the effects of nitroprusside or prostacyclin (NP/Prost) on regional pulmonary blood flow (rPBF) in 21 dogs after oleic acid- (OA) induced acute pulmonary edema and compared the results with data from 11 dogs given OA only and 5 given meclofenamate after OA. After OA only, a progressive decrease in rPBF occurred in edematous gravity-dependent lung regions, but only in 6 of 11 dogs. In these six dogs, rPBF fell 41 +/- 12% compared with base line or with the other five dogs (3 +/- 19%) (P less than 0.05). In the NP/Prost group, the vasodilators failed to reverse any change in rPBF after OA but did prevent additional derecruitment until the drug infusion was stopped, after which rPBF to the edematous regions decreased further. In contrast, meclofenamate after OA temporally accelerated but did not quantitatively enhance rPBF reduction in edematous lung regions. Thus, in this model, vessels in edematous lung regions remain vasoreactive only until derecruited. We speculate that the mechanism of derecruitment involves an interaction between edema accumulation and vasoconstriction, in which the actual pattern of rPBF after lung injury represents a balance between mechanisms responsible for vascular derecruitment and vasodilation from prostacyclin production.     

Injury in nonischemic lung after unilateral pulmonary ischemia with reperfusion.

We developed an in vivo intact canine model to study pulmonary ischemia-reperfusion (IR) injury. The surgical approach simulates that of unilateral lung transplantation but is free of technical difficulties and other factors related to lung preservation. Serial measurements of regional pulmonary blood flow (rPBF), extravascular density (EVD), and transcapillary protein flux were made with the quantitative imaging technique of positron emission tomography. Eleven experimental and six control animals were studied. After 2 h of warm ischemia followed by reperfusion, no significant change occurred in rPBF despite significantly increased EVD, which was greater on the ischemic than on the nonischemic side. Protein flux, measured as a rate constant, was also greater on the ischemic than on the nonischemic side (median 181 x 10(-4)/min, range 104-619, vs. median 90, range 33-132) immediately after reperfusion. Both sides were also significantly different from control values (median 37, range 21-57). On both sides, protein flux decreased over time and at 5 h after reperfusion was not different from that of controls. Data from the control animals showed that these findings in the experimental animals were not due to surgical technique, deterioration in the surgical preparation, or hyperperfusion of the nonischemic lung. Thus IR injury of one lung can lead to similar, but less severe, injury in the contralateral lung. Because injury in the nonischemic lung develops only after reperfusion of the ischemic lung, injury to the nonischemic lung is probably humorally mediated. The model is a useful and relevant method for studying the physiological consequences of pulmonary IR injury.     

Allowance for random dose estimation errors in atomic bomb survivor studies: a revision

Allowing for imprecision of radiation dose estimates for A-bomb survivors followed up by the Radiation Effects Research Foundation can be improved through recent statistical methodology. Since the entire RERF dosimetry system has recently been revised, it is timely to reconsider this. We have found that the dosimetry revision itself does not warrant changes in these methods but that the new methodology does. In addition to assumptions regarding the form and magnitude of dose estimation errors, previous and current methods involve the apparent distribution of true doses in the cohort. New formulas give results conveniently and explicitly in terms of these inputs. Further, it is now possible to use assumptions about two components of the dose errors, referred to in the statistical literature as "classical" and "Berkson-type". There are indirect statistical indications, involving non-cancer biological effects, that errors may be somewhat larger than assumed before, in line with recommendations made here. Inevitably, methods must rely on uncertain assumptions about the magnitude of dose errors, and it is comforting to find that, within the range of plausibility, eventual cancer risk estimates are not very sensitive to these.     

Leukotriene inhibitors do not block hypoxic pulmonary vasoconstriction in dogs

We studied whether intravenously administered inhibitors of leukotriene synthesis (diethylcarbamazine, DEC) or end-organ effect (FPL-55712) would change the distribution of regional pulmonary blood flow (rPBF) caused by left lower lobe (LLL) alveolar hypoxia in dogs. Both drugs failed to alter rPBF. In addition, the pressor response to whole-lung hypoxia was not blocked by an FPL-55712 infusion. On the other hand, nitroprusside, as a nonspecific vasodilator also administered intravenously, was able to partially reverse the effects of LLL hypoxia on rPBF. Thus our data do not support a role for leukotriene mediation of hypoxic pulmonary vasoconstriction in dogs.     

Positron emission tomography: imaging and quantification of neurotransporter availability

Over the last decade, a large number of radiotracers have been developed to image and quantify transporter availability with positron emission tomography (PET) or single-photon emission computed tomography (SPECT). Radiotracers suitable to image dopamine transporters (DATs) and serotonin transporters (SERTs) have been the object of most efforts. Following a brief overview of DAT and SERT radiotracers that have been demonstrated to be suitable for quantitative analysis in vivo, this article describes the principal methods that have been used for the analysis of these data. Kinetic modeling is the most direct implementation of the compartment models, but with some tracers accurate input function measurement and good compartment configuration identification can be difficult to obtain. Other methods were designed to overcome some particular vulnerability to error of classic kinetic modeling, but introduced new vulnerabilities in the process. Reference region methods obviate the need for arterial plasma measurement, but are not as robust to violations of the underlying modeling assumptions as methods using the arterial input function. Graphical methods give estimates of distribution volumes without the requirement of compartment model specification, but provide a biased estimator in the presence of statistical noise. True equilibrium methods are quite robust, but their use is limited to experiments with tracers that are suitable for constant infusion. In conclusion, no universally "best" method is applicable to all neurotransporter imaging studies, and careful evaluation of model-based methods is required for each radiotracer.     

Quantitative Amyloid Imaging Using Image-Derived Arterial Input Function

Amyloid PET imaging is an indispensable tool widely used in the investigation, diagnosis and monitoring of Alzheimer’s disease (AD). Currently, a reference region based approach is used as the mainstream quantification technique for amyloid imaging. This approach assumes the reference region is amyloid free and has the same tracer influx and washout kinetics as the regions of interest. However, this assumption may not always be valid. The goal of this work is to evaluate an amyloid imaging quantification technique that uses arterial region of interest as the reference to avoid potential bias caused by specific binding in the reference region. 21 participants, age 58 and up, underwent Pittsburgh compound B (PiB) PET imaging and MR imaging including a time-of-flight (TOF) MR angiography (MRA) scan and a structural scan. FreeSurfer based regional analysis was performed to quantify PiB PET data. Arterial input function was estimated based on coregistered TOF MRA using a modeling based technique. Regional distribution volume (V_T) was calculated using Logan graphical analysis with estimated arterial input function. Kinetic modeling was also performed using the estimated arterial input function as a way to evaluate PiB binding (DVR_kinetic) without a reference region. As a comparison, Logan graphical analysis was also performed with cerebellar cortex as reference to obtain DVR_REF. Excellent agreement was observed between the two distribution volume ratio measurements (r>0.89, ICC>0.80). The estimated cerebellum V_T was in line with literature reported values and the variability of cerebellum V_T in the control group was comparable to reported variability using arterial sampling data. This study suggests that image-based arterial input function is a viable approach to quantify amyloid imaging data, without the need of arterial sampling or a reference region. This technique can be a valuable tool for amyloid imaging, particularly in population where reference normalization may not be accurate.     

Eicosanoid balance and perfusion redistribution of oleic acid-induced acute lung injury.

We have proposed that endogenous prostacyclin opposes the vasoconstriction responsible for redistribution of regional pulmonary blood flow (rPBF) away from areas of increased regional lung water concentration (rLWC) in canine oleic acid- (OA) induced acute lung injury (D. P. Schuster and J. Haller. J. Appl. Physiol. 69: 353-361, 1990). To test this hypothesis, we related regional lung tissue concentrations of 6-ketoprostaglandin (PG) F1 alpha and thromboxane (Tx) B2 in tissue samples obtained 2.5 h after administration of OA (0.08 ml/kg iv) to rPBF and rLWC measured by positron emission tomography. After OA only (n = 16), rLWC increased in dependent lung regions. Some animals responded to increased rLWC by redistribution of rPBF away from the most edematous regions (OA-R, n = 6), whereas others did not (OA-NR, n = 10). In another six animals, meclofenamate was administered after OA (OA-meclo). After OA, tissue concentrations of 6-keto-PGF1 alpha were greater than TxB2 in all groups, but concentrations of 6-keto-PGF1 alpha were not different between OA-R and OA-NR animals. TxB2 was increased in the dependent regions of animals in both OA-R and OA-NR groups compared with controls (no OA, n = 4, P < 0.05). The tissue TxB2/6-keto-PGF1 alpha ratio was smaller in controls and OA-NR in which no perfusion redistribution occurred than in OA-R and OA-meclo in which it did occur. This TxB2/6-keto-PGF1 alpha ratio correlated significantly with the magnitude of perfusion redistribution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Threshold and other departures from linear-quadratic curvature in the non-cancer mortality dose-response curve in the Japanese atomic bomb survivors

Recently released data on non-cancer mortality in Japanese atomic bomb survivors are analysed using a variety of generalised relative risk models that take account of errors in estimates of dose to assess the dose-response at low doses. If linear-threshold, quadratic-threshold or linear-quadratic-threshold relative risk models (the dose-response is assumed to be linear, quadratic or linear-quadratic above the threshold, respectively) are fitted to the non-cancer data there are no statistically significant (p>0.10) indications of threshold departures from linearity, quadratic curvature or linear-quadratic curvature. These findings are true irrespective of the assumed magnitude of dosimetric error, between 25%–45% geometric standard deviations. In general, increasing the assumed magnitude of dosimetric error had little effect on the central estimates of the threshold, but somewhat widened the associated confidence intervals. If a power of dose model is fitted, there is little evidence (p>0.10) that the power of dose in the dose-response is statistically significantly different from 1, again irrespective of the assumed magnitude of dosimetric errors in the range 25%–45%. Again, increasing the size of the errors resulted in wider confidence intervals on the power of dose, without marked effect on the central estimates. In general these findings remain true for various non-cancer disease subtypes.     

TEP/TDM au FDG et toxicité pulmonaire à la bléomycine : à propos d’un cas clinique

Patients treated with bleomycin should be frequently monitored during and after treatment. Actually this treatment can cause pulmonary toxicity and may progress to pulmonary fibrosis. Extreme care is required in patients with a severe deterioration of renal function or impaired lung function. PET/CT can be a useful tool for the early diagnosis of this complication. We report a case of bleomycin-induced pneumonitis and discovered during a PET/CT performed for evaluation of Hodgkin's disease.     

Measurement of glucose consumption using [(18)F]fluorodeoxyglucose

The [(18)F]fluorodeoxyglucose (FDG) method to measure glucose metabolism quantitatively in humans is reviewed. The assumptions and the mathematical formulation of the underlying autoradiographic Sokoloff model and its adaptation to positron emission tomography (PET) are described. Various implementations to estimate glucose consumption from measured tissue activity with PET are presented. The dependence on the "lumped constant" and on the accuracy of the input function is discussed. Recommendations for the practical application of different procedures for performing FDG studies are given.     

The low specificity of postoperative perfusion lung scan defects.

Ventilation and perfusion lung scans were performed preoperatively and postoperatively in 169 patients and classified blindly according to preset criteria. Perfusion lung scan abnormalities were present in 25 (15%) of the preoperative scans and 42 (25%) of the postoperative scans; 16 (38%) of the 42 abnormal postoperative scans were identical to the preoperative scans. Perfusion defects indicating a "high probability" of pulmonary embolism (lobar or segmental defects) were present in 5 preoperative scans and 10 postoperative scans; the 10 postoperative scans were classified as showing "definite" (5), "possible" (1) or "no" (4) pulmonary embolism on the basis of the preoperative scan and the ventilation scan; none of the 10 patients had clinical evidence of pulmonary embolism. Venous thrombosis was present in 12 patients, including 4 of the patients whose lung scans showed definite pulmonary embolism. Thus, postoperative perfusion lung scan defects are potentially misleading even when large.     

A New Method of Detecting Pulmonary Nodules with PET/CT Based on an Improved Watershed Algorithm

Background

Integrated ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is widely performed for staging solitary pulmonary nodules (SPNs). However, the diagnostic efficacy of SPNs based on PET/CT is not optimal. Here, we propose a method of detection based on PET/CT that can differentiate malignant and benign SPNs with few false-positives.

Method

Our proposed method combines the features of positron-emission tomography (PET) and computed tomography (CT). A dynamic threshold segmentation method was used to identify lung parenchyma in CT images and suspicious areas in PET images. Then, an improved watershed method was used to mark suspicious areas on the CT image. Next, the support vector machine (SVM) method was used to classify SPNs based on textural features of CT images and metabolic features of PET images to validate the proposed method.

Results

Our proposed method was more efficient than traditional methods and methods based on the CT or PET features alone (sensitivity 95.6%; average of 2.9 false positives per scan).     

Evaluating pulmonary vascular permeability with radiolabeled proteins: an error analysis

Using techniques of mathematical simulation, we compared two methods of evaluating pulmonary vascular permeability, i.e., transvascular protein flux. Both methods calculate a transport rate constant [pulmonary transcapillary escape rate (PTCER)] after making external radiation detection measurements of an intravenously administered radiolabeled protein. With one method, lung tissue time-activity data are acquired by positron emission tomography (PET) and are interpreted with a two-compartment model. With the other method, the time-activity data are acquired with simple detector probes and are interpreted by linear regression after normalizing for various physical factors (slope-intercept or SI method). The results show that significant errors in calculating PTCER can result from using the SI method, because it ignores the effects of back-flux on the tissue time-activity measurements. Both methods produce errors if the data analysis includes activity from vascular volumes not involved in tracer exchange with the extravascular compartment. Significant errors can also occur with the PET method, particularly when permeability is nearly normal, if pulmonary vascular volume changes significantly during the period of data collection. On balance, the PET method appears to be the method of choice for accurately evaluating pulmonary vascular permeability by protein flux measurements, although both methods may be useful in clinical applications.     

Microcirculation impedance analysis in cat lung

An analysis of pulsatile microcirculation in cat lung, with special attention to the pulmonary microvascular impedance, is presented. A theoretical calculation is made on the basis of a complete set of experimental data on the morphology and elasticity of cat's pulmonary capillary sheets. The transfer matrix of the pulmonary microvascular impedance is obtained. The input impedance at the capillary entrance and exit are determined. The input impedance at the pulmonary arterial trunk is compared under various physiological conditions. It is shown that although the impact of pulmonary microcirculation on the relationship between the steady mean flow and pressure in the pulmonary arteries and veins is decisively large, the influence of the alveolar microcirculation on the input impedance at the pulmonary arterial trunk is small.     

Pulmonary veno-occlusive disease as a cause of severe pulmonary hypertension in a dog

Background

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary arterial hypertension (PAH) in humans and can be classified in idiopathic, heritable, drug and radiation-induced, and associated with connective tissue disease or human immunodeficiency virus infection. Recently, biallelic mutations of the EIF2AK4 gene have been discovered as a cause for an autosomal recessive form of PVOD in humans. In dogs, PAH is poorly characterized and is generally considered to be idiopathic or secondary to (for example) congenital left-to right cardiovascular shunts or heartworm disease. However, recently, the pathologic features resembling human PVOD were retrospectively described in post-mortem lung samples of dogs presenting with respiratory distress and idiopathic pulmonary hypertension (PH), which suggests that PVOD contributes to an unknown percentage of cases with unexplained PH. In dogs, information on the clinical presentation of PVOD is scarce and the cause and pathogenesis of this disease is still unknown.

Case presentation

An 11-year-old, intact male German Shepherd dog (GSD) was presented with a 2-day history of acute-onset dyspnea and generalized weakness. Physical examination, laboratory analysis, thoracic radiography, echocardiography, a computed tomography scan and an ante mortem lung biopsy demonstrated severe arterial hypoxemia and severe PH but were not diagnostic for a known disease syndrome. Based on the poor reaction to therapy with oxygen, sildenafil, pimobendan and dexamethasone the dog was euthanized. Histopathology of the lungs showed venous and arterial remodelling, segmental congestion of alveolar capillaries and foci of vascular changes similar to human pulmonary capillary hemangiomatosis, indicating that the dog suffered from PVOD. Whole genome sequencing analysis was performed on the case and a healthy GSD. Validation was performed by Sanger sequencing of five additional GSD's unknown for any form of respiratory stress and aged ≥?10 years. No causal variants were found in the genes that are known to be involved in human PVOD and PAH.

Conclusions

This case report confirms that PVOD should be a diagnostic consideration in dogs presenting with dyspnea and unexplained PH. In the present case, no casual genetic mutations known to be involved in humans with PVOD and PAH were found.

     

18F-FDG PET 和治疗量131I 全身扫描对分化型甲 状腺癌根治术后转移灶检测的临床价值评估

目的:探讨18F-FDG PET显像和131I-全身扫描(131I-WBS)SPECT显像对分化型甲状腺癌(DTC)术后转移灶的临床诊断价值。方法:对57例外科术后拟行131I治疗的DTC患者行18F-FDG PET全身显像和131I-WBS扫描,观察和记录在糖代谢和碘代谢中DTC转移灶的定位及数量变化,并同时测定甲状腺球蛋白(Tg),促甲状腺激素释放激素(TSH)等实验室检查项目。结果:57例DTC患者18F-FDG PET显像发现真阳性20例、假阳性3例、真阴性31例、假阴性3例,其灵敏度为87.0%,特异性为91.2%。而131I-WBS扫描发现真阳性13例、假阳性2例、真阴性34例、假阴性8例,其灵敏度为61.9%,特异性为94.4%。PET显像和131I-WBS扫描共检出阳性病灶73个,其中淋巴结32个,肺5个,纵隔6个,骨26个,其他部位4个。PET显像发现43个阳性病灶(58.9%),而131I-WBS检出30个(41.1%)。当Tg水平>10μg/L时,随着Tg在血清含量的增高,两种显像方法的对DTC转移灶的阳性检出率亦随之升高。结论:两种检查对DTC术后转移灶的监测和131I的治疗具有良好的互补性,18F-FDG PET显像在Tg阳性和131I-WBS阴性的患者的转移灶检出上更具有优势,有重要的临床指导意义。     

Perfusion Lung Scans Provide a Guide to Which Patients With Apparent Primary Pulmonary Hypertension Merit Angiography

There is hesitancy, based on the perceived risk, to do pulmonary angiography in patients believed to have primary pulmonary hypertension. Yet pulmonary hypertension due to major-vessel, chronic thromboembolism mimics primary pulmonary hypertension clinically and on standard laboratory tests. Because thromboembolic pulmonary hypertension is potentially remediable by thromboendarterectomy and primary pulmonary hypertension is not, differentiating between these disorders is essential. Angiography is required in patients with thromboembolic pulmonary hypertension to define the anatomic location of the thrombi. In evaluating perfusion lung scans of 110 patients with pulmonary hypertension to determine whether the scan might provide a guide to selecting those patients who merit angiography, no segmentalsize perfusion defects were noted on the scans of 64 patients with primary pulmonary hypertension, whereas all 46 patients with thromboembolic hypertension had one or more defects that were segmental in size or larger. These data indicate that a perfusion lung scan should be done in patients with pulmonary hypertension of uncertain cause and that those with one or more segmental or larger defects merit pulmonary angiography before being diagnosed as having primary pulmonary hypertension.     

Respiratory Motion Reduction in PET/CT Using Abdominal Compression for Lung Cancer Patients

Purpose

Respiratory motion causes substantial artifacts in reconstructed PET images when using helical CT as the attenuation map in PET/CT imaging. In this study, we aimed to reduce the respiratory artifacts in PET/CT images of patients with lung tumors using an abdominal compression device.

Methods

Twelve patients with lung cancer located in the middle or lower lobe of the lung were recruited. The patients were injected with 370 MBq of ¹⁸F-FDG. During PET, the patients assumed two bed positions for 1.5 min/bed. After conducting free-breathing imaging, we obtained images of the patients with abdominal compression by applying the same setup used in the free-breathing scan. The differences in the standardized uptake value (SUV)_max, SUV_mean, tumor volume, and the centroid of the tumors between PET and various CT schemes were measured.

Results

The SUV_max and SUV_mean derived from PET/CT imaging using an abdominal compression device increased for all the lesions, compared with those obtained using the conventional approach. The percentage increases were 18.1% ±14% and 17% ±16.8% for SUV_max and SUV_mean, respectively. PET/CT imaging combined with abdominal compression generally reduced the tumor mismatch between CT and the corresponding attenuation corrected PET images, with an average decrease of 1.9±1.7 mm over all the cases.

Conclusions

PET/CT imaging combined with abdominal compression reduces respiratory artifacts and PET/CT misregistration, and enhances quantitative SUV in tumor. Abdominal compression is easy to set up and is an effective method used in PET/CT imaging for clinical oncology, especially in the thoracic region.     

The parameter identification problem for the somatic shunt model

The somatic shunt model, a generalized version of the Rall equivalent cylinder model, is used commonly to describe the passive electrotonic properties of neurons. Procedures for determining the parameters of the somatic shunt model that best describe a given neuron typically rely on the response of the cell to a small step of hyperpolarizing current injected by an intrasomatic recording electrode. In this study it is shown that the problem of estimating model parameters for the somatic shunt model using physiological data is ill-posed, in that very small errors in measured data can lead to large and unpredictable errors in parameter estimates. If the somatic shunt is assumed to be a real property of the intact neuron, the effects of these errors are not severe when predicting EPSP waveshapes resulting from synaptic input at a given location. However, if the somatic shunt is assumed to be a consequence of a leakage pathway around the recording electrode, and a correction for the shunt is applied, then the instability of the inverse problem can introduce large errors in estimates of EPSP waveshape as a function of synaptic location in the intact cell. Morphological constraints can be used to improve the accuracy of the inversion procedure in terms of both parameter estimates and predicted EPSP responses.     

Lung Perfusion Scanning in Hepatic Cirrhosis

Abnormal lung perfusion scans using radioactive particles were found in five out of six cases of hepatic cirrhosis with arterial hypoxaemia. None had clinical evidence of cardiopulmonary disease or signs of pulmonary embolism on arteriography. The scan defects are probably caused by a disorder of the pulmonary microvasculature, which may show regional variation in severity.