Effects of aerobic exercise training on brain structure and psychological well-being in young adults.

AIM: There is convergent evidence that exercise increases psychological well-being; however, the mechanism of this psychological effect of exercise is not yet completely understood. The purpose of this study was to examine the effects of aerobic exercise training on brain structure and psychological well-being in young adults. METHODS: University students who had not regularly exercised were divided into training group (N.=15) and control group (N.=15). The training group performed a total 30 periods of aerobic exercise training, while the control group never performed. Whole-brain magnetic resonance imaging scans and mental health questionnaire examinations were performed before and after the exercise training period for all of the participants. A voxel-based morphometry (VBM) analysis was used to compare the changes in gray-matter volumes in the two groups. VBM is an objective whole-brain technique for characterization of regional cerebral volume and tissue concentration differences in structural magnetic resonance images. RESULTS: The results of VBM analysis revealed no change in gray-matter volume in the training group, although the gray-matter volume of the left insula was significantly decreased in the control group after the exercise training period. The training group exhibited significant improvement in some scores on the mental health questionnaire after the exercise training period, compared with the control group. CONCLUSIONS: These findings suggest that aerobic exercise training may inhibit gray-matter volume loss in the insula, and that a relationship may exist between preservation of insula gray-matter and improvement of psychological well-being by aerobic exercise training.

Hypoperfusion in the supplementary motor area, dorsolateral prefrontal cortex and insular cortex in Parkinson's disease.

The changes of regional cerebral blood flow (rCBF) in Parkinson's disease (PD) were investigated. Because of individual differences in brain volume and the extent of brain atrophy, previous functional imaging studies involved potential methodological difficulties. In this study, using the statistical parametric mapping technique, 99mTechnetium-labeled hexamethylpropyleneamineoxime brain single-photon emission computed tomography images from 18 patients with PD were transformed into standard brain-based stereotaxic coordinate spaces and then compared with such images for 11 control subjects matched for age and extent of brain atrophy. A rCBF decrement in the supplementary motor area (SMA) and such decrement in the dorsolateral prefrontal cortex (DLPFC) were observed in the summarized PD images as compared with controls (p<0.005). In a subgroup in the Hoehn-Yahr III/IV stage (11 cases), the rCBF decrement was demonstrated not only in the SMA, but also in the DLPFC and insular cortex (p<0.001). There was a correlation between the degree of the rCBF decrement in the DLPFC or the insular cortex and the score of the unified Parkinson's disease rating scale (p<0.05), while the rCBF decrement in the SMA showed no relationship with the severity of disease. The function of the SMA is closely associated with the nigro-striatal pathway and its impairment can explain the basic akinetic symptoms in PD, which are responsive to L-DOPA treatment. On the other hand, the DLPFC and insular cortex may play key roles in specific symptoms of impairment at advanced stages, such as impaired working memory, postural instability and autonomic dysfunction. We hypothesize that the impairment of the DLPFC and insular function is correlated with the progression of the disease and is related to DOPA-refractory symptoms, which are major problems in the care of patients with advanced PD.

Visual recognition: evidence for two distinctive mechanisms from a PET study.

In this study, we examined the hypothesis that two distinct sets of cortical areas subserve two dissociable neurophysiological mechanisms of visual recognition. We posited that one such mechanism uses category specific cues extractable from the viewed pattern for the purpose of recognition. The other mechanism matches the pattern to be recognized with a pre-encoded memory representation of the pattern. In order to distinguish the cortical areas active in these two strategies, we measured changes in regional cerebral blood flow (rCBF) with positron emission tomography (PET) and (15)O Butanol as the radiotracer. Ten subjects performed pattern recognition tasks based on three different short-term memory conditions and a condition based on visual categories of the patterns. When subjects used representations of the patterns held in short-term memory for the purpose of recognition, the precunei were bilaterally activated. Recognition based on visual categories of the patterns activated the right (R) angular gyrus, left (L) inferior temporal gyrus, and L superior parieto-occipital cortex. These findings demonstrate that the R angular gyrus, the L inferior temporal gyrus, and the L superior parieto-occipital cortex are associated with recognition of patterns based on visual categories, whereas recognition of patterns using memory representations is associated with the activity of the precunei. This study is the first to show functional dual dissociation of active cortical fields for different mechanisms of visual pattern recognition.

A PET study of visuomotor learning under optical rotation.

We measured the regional cerebral blood flow (rCBF) in six healthy volunteers with PET (positron emission tomography) and H(15)(2)O to identify the areas of the human brain involved in sensorimotor learning. The learning task was visually guided reaching with sensorimotor discrepancy caused by optical rotation. PET measurements were performed in the early and late stages of the adaptation to the sensorimotor perturbation. Control measurements were obtained during an eye movement task and a reaching task without optical rotation. The rCBF data of each learning stage were compared to those of both control conditions. During the early stage, rCBF increases were detected in the rostral premotor cortex bilaterally, the posterior part of the left superior parietal lobule (SPL), and the right SPL including the intraparietal sulcus (IPS). During the late stage, rCBF increases were detected in the left caudal premotor area, the left supplementary motor area proper, the left SPL, the right SPL including the IPS, and the right postcentral sulcus extending to the inferior parietal lobule. These results reveal that sensorimotor learning accompanies changes in the recruited cortical areas during different stages of the adaptation, reflecting the different functional roles of each area for different components of adaptation, from learning of new sensorimotor coordination to retention or retrieval of acquired coordination.

Fast reaction to different sensory modalities activates common fields in the motor areas, but the anterior cingulate cortex is involved in the speed of reaction.

We examined which motor areas would participate in the coding of a simple opposition of the thumb triggered by auditory, somatosensory and visual signals. We tested which motor areas might be active in response to all three modalities, which motor structures would be activated specifically in response to each modality, and which neural populations would be involved in the speed of the reaction. The subjects were required to press a button with their right thumb as soon as they detected a change in the sensory signal. The regional cerebral blood flow (rCBF) was measured quantitatively with (15)O-butanol and positron emission tomography (PET) in nine normal male subjects. Cytoarchitectural areas were delimited in 10 post mortem brains by objective and quantitative methods. The images of the post mortem brains subsequently were transformed into standard anatomic format. One PET scanning for each of the sensory modalities was done. The control condition was rest with the subjects having their eyes closed. The rCBF images were anatomically standardized, and clusters of significant changes in rCBF were identified. These were localized to motor areas delimited on a preliminary basis, such as supplementary motor area (SMA), dorsal premotor zone (PMD), rostral cingulate motor area (CMAr), and within areas delimited by using microstructural i.e., cytoarchitectonic criteria, such as areas 4a, 4p, 3a, 3b, and 1. Fields of activation observed as a main effect for all three modalities were located bilaterally in the SMA, CMAr, contralateral PMD, primary motor (M1), and primary somatosensory cortex (SI). The activation in M1 engaged areas 4a and 4p and expanded into area 6. The activation in SI engaged areas 3b, 1, and extended into somatosensory association areas and the supramarginal gyrus posteriorly. We identified significant activations that were specific for each modality in the respective sensory association cortices, though no modality specific regions were found in the motor areas. Fields in the anterior cingulate cortex, rostral to the CMAr, consistently showed significant negative correlation with mean reaction time (RT) in all three tasks. These results show that simple reaction time tasks activate many subdivisions of the motor cortices. The information from different sensory modalities converge onto the common structures: the contralateral areas 4a, 4p, 3b, 1, the PMD, and bilaterally on the SMA and the CMAr. The anterior cingulate cortex might be a key structure which determine the speed of reaction in simple RT tasks.

Analysis of time-density curves of contrast media for improvement of chest dynamic incremental CT.

PURPOSE: The goal of this work was to analyze time-density curves (TDCs) of contrast media (CM) in the mediastinal vasculature to optimize chest dynamic incremental CT. METHOD: Forty-three patients were injected with nonionic CM into the forearm veins with injection rates (ml/s), durations (s), and total amounts (ml) of 2.0, 20, and 40 (protocol 1); 4.0, 20, and 80 (protocol 2); and 2.0, 40, and 80 (protocol 3). TDCs were obtained for the pulmonary trunk (PA) and ascending (AA) and descending (DA) aorta from dynamic scans. Areas under the curves (AUCs) of TDCs for imaginary 30 s scans were evaluated. RESULTS: AUC peaks were obtained after 10, 17, and 19 s (PA, AA and DA; protocol 1; 9, 16, and 18 s (protocol 2); and 18, 25, and 28 s (protocol 3) delay time. CONCLUSION: Better chest dynamic incremental CT would be expected with scan midpoints a little after the end of injection of CM.

Human cortical areas activated in relation to vergence eye movements-a PET study.

Human cortical areas activated in relation to vergence eye movements were determined using positron emission tomography. Binocular disparity-driven visual stimuli were presented using a head-mounted display. Eye movements were monitored continuously by an infrared limbus tracker. A combination of a bar and a cross was used as the target. In the vergence task, subjects were instructed to follow an approaching bar, while ignoring a stationary cross. Activation in relation to vergence eye movement was discriminated from activation in relation to motion vision by using the ignore-bar task as the control. In the ignore-bar task, subjects were instructed to fixate on a stationary cross, while ignoring an approaching bar. The fixation task was used as the basic control for both the vergence and the ignore-bar tasks. Areas of activation in relation to vergence eye movements were found in the bilateral temporooccipital junction, the left inferior parietal lobule, and the right fusiform gyrus by comparing regional cerebral flow between the vergence and ignore-bar tasks and by the conjunctive analyses of vergence-vs-ignore comparison with vergence-vs-fixation comparison.

Tc-99m HMPAO SPECT in the evaluation of Alzheimer's disease: correlation between neuropsychiatric evaluation and CBF images.

The purpose of this study was to evaluate the effects of various covariants on the distribution pattern of Tc-99m HMPAO in patients with Alzheimer's disease by correlation analysis. Twenty patients with Alzheimer's disease and 15 age matched normal subjects participated. Tc-99m HMPAO brain SPECT and x ray computed tomography (CT) were acquired for each subject. SPECT images were transformed to a standard size and shape by automated image registration (AIR) and were used for group comparison by means of SPM96. Voxel based covariance analysis was performed on standardised images taking the age of patients, severity of disease (clinical dementia rating scale, mini mental state examination, physical self maintenance scale), and atrophy indices as variables. There was significantly decreased regional cerebral blood flow (rCBF) in the frontal, parietal, and temporal regions in the patient group (p<0.001), more marked in those patients having severe dementia. Covariance analysis disclosed that aging and severity of disease have a pronounced effect on rCBF, especially that of the left parietal region.

Parametric mapping of cerebral blood flow deficits in Alzheimer's disease: a SPECT study using HMPAO and image standardization technique.

UNLABELLED: This study assessed the accuracy and reliability of Automated Image Registration (AIR) for standardization of brain SPECT images of patients with Alzheimer's disease (AD). Standardized cerebral blood flow (CBF) images of patients with AD and control subjects were then used for group comparison and covariance analyses. METHODS: Thirteen patients with AD at an early stage (age 69.8+/-7.1 y, Clinical Dementia Rating Score 0.5-1.0, Mini-Mental State Examination score 19-23) and 20 age-matched normal subjects (age 69.5+/-8.3 y) participated in this study. 99mTc-hexamethyl propylenamine oxime (HMPAO) brain SPECT and CT scans were acquired for each subject. SPECT images were transformed to a standard size and shape with the help of AIR. Accuracy of AIR for spatial normalization was evaluated by an index calculated on SPECT images. Anatomical variability of standardized target images was evaluated by measurements on corresponding CT scans, spatially normalized using transformations established by the SPECT images. Realigned brain SPECT images of patients and controls were used for group comparison with the help of statistical parameter mapping. Significant differences were displayed on the respective voxel to generate three-dimensional Z maps. CT scans of individual subjects were evaluated by a computer program for brain atrophy. Voxel-based covariance analysis was performed on standardized images with ages and atrophy indices as independent variables. RESULTS: Inaccuracy assessed by functional data was 2.3%. The maximum anatomical variability was 4.9 mm after standardization. Z maps showed significantly decreased regional CBF (rCBF) in the frontal, parietal and temporal regions in the patient group (P < 0.001). Covariance analysis revealed that the effects of aging on rCBF were more pronounced compared with atrophy, especially in intact cortical areas at an early stage of AD. Decrease in rCBF was partly due to senility and atrophy, however these two factors cannot explain all the deficits. CONCLUSION: AIR can transform SPECT images of AD patients with acceptable accuracy without any need for corresponding structural images. The frontal regions of the brain, in addition to parietal and temporal lobes, may show reduced CBF in patients with AD even at an early stage of dementia. The reduced rCBF in the cortical regions cannot be explained entirely by advanced atrophy and fast aging process.

Detection of CBF deficits in neuropsychiatric disorders by an expert system: a 99Tcm-HMPAO brain SPET study using automated image registration.

The aims of this study were to develop an objective method for assessing rCBF deficits using a statistical image analysis protocol and to validate its effective use in clinical practice. 99Tcm-HMPAO brain SPET images were acquired for 40 normal subjects, 10 patients with Alzheimer's disease and 10 patients with depression. Automated image registration was used to standardize the size and shape of the brain structures for all subjects. The images of the first 30 normal subjects were used to construct a normal database. The CBF images of the other 10 normal subjects and the 20 patients were compared voxel by voxel with the normal database to map CBF abnormalities by statistical evaluation. The results were compared with the clinical reports of CBF images. The expert system detected all rCBF deficits reported by the nuclear physicians. Some additional areas with special information, like atrophy and bilateral asymmetry, were also identified by the expert system. We conclude that this expert system can delineate CBF deficits with sufficiently high accuracy, differentiating normal from abnormal CBF images using voxel-based comparisons. The use of an expert system improves rCBF SPET image evaluation.

Oculomotor sequence learning: a positron emission tomography study.

The purpose of this study was to identify the brain regions activated in relation to oculomotor sequence learning. Nine healthy subjects participated in the study, which consisted of three positron emission tomography scans. In the initial learning task, subjects were instructed to track a sequence of seven successive positions of visual targets and to memorize the order of the targets as well as their spatial locations. In the saccade task, subjects were instructed to track visual targets presented at random locations. In the control task, subjects were instructed to gaze at a fixation point. Fields showing significant regional cerebral blood flow change were determined from task-minus-control subtraction images. We determined that fields in the pre-supplementary motor area (pre-SMA), the intraparietal cortex, and the prefrontal cortex were activated not only in the learning-minus-control images but also in the learning-minus-saccade images. Although prefrontal and parietal activations were bilateral, pre-SMA activation was confined to the left hemisphere. The results indicate that these fields function as a part of the neural network involved in the learning of sequential saccadic eye movements.

Use of automated image registration to generate mean brain SPECT image of Alzheimer's patients.

UNLABELLED: The purpose of this study was to compute and compare the group mean HMPAO brain SPECT images of patients with senile dementia of Alzheimer's type (SDAT) and age matched control subjects after transformation of the individual images to a standard size and shape. METHODS: Ten patients with Alzheimer's disease (age 71.6 +/- 5.0 yr) and ten age matched normal subjects (age 71.0 +/- 6.1 yr) participated in this study. Tc-99m HMPAO brain SPECT and X-ray CT scans were acquired for each subject. SPECT images were normalized to an average activity of 100 counts/pixel. Individual brain images were transformed to a standard size and shape with the help of Automated Image Registration (AIR). Realigned brain SPECT images of both groups were used to generate mean and standard deviation images by arithmetic operations on voxel based numerical values. Mean images of both groups were compared by applying the unpaired t-test on a voxel by voxel basis to generate three dimensional T-maps. X-ray CT images of individual subjects were evaluated by means of a computer program for brain atrophy. RESULTS: A significant decrease in relative radioisotope (RI) uptake was present in the bilateral superior and inferior parietal lobules (p < 0.05), bilateral inferior temporal gyri, and the bilateral superior and middle frontal gyri (p < 0.001). The mean brain atrophy indices for patients and normal subjects were 0.853 +/- 0.042 and 0.933 +/- 0.017 respectively, the difference being statistically significant (p < 0.001). CONCLUSION: The use of a brain image standardization procedure increases the accuracy of voxel based group comparisons. Thus, intersubject averaging enhances the capacity for detection of abnormalities in functional brain images by minimizing the influence of individual variation.

PET study of pointing with visual feedback of moving hands.

This study was conducted to determine where in the human brain visual feedback of hand movements is processed to allow accurate pointing. Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and H2 15O in nine normal volunteers while performing one control and two reaching tasks. In all tasks, visual stimuli were presented on a head mounted display (HMD). A target board was placed in front of the subjects bearing six red light-emitting diodes (LEDs) aligned on a circle with a green LED at its center. The center green LED and one of the six red LEDs, randomly selected, were repeatedly switched on and off, alternatively. In the control task, subjects were instructed to gaze at the lit LED. In the two reaching tasks, the reaching with visual feedback (RwithF) task and the reaching without visual feedback (RwithoutF) task, they had to point to the lit red LED with their right index fingers. In the RwithF task, their right hands were visible on the HMD before touching the target, whereas in the RwithoutF task, they were not visible. For each subject, subtraction images of each reaching task minus the control and the RwithF task minus the RwithoutF task were calculated after transformation of PET images into the standard brain shape with an adjustable computerized brain atlas. These subtraction rCBF images were then averaged among the subjects, and significant changes of rCBF were identified. Significant increases in rCBF not only in the RwithF task minus control image but also in the RwithF task minus the RwithoutF task image were observed in the supramarginal cortex, the premotor cortex and the posterior cingulate cortex of the left hemisphere, the caudate nucleus and the thalamus of the right hemisphere, and the right cerebellum and vermis. These results indicate that the supramarginal cortex, the premotor cortex, and the posterior cingulate cortex of the left hemisphere and the cerebellum are involved in integrating visual feedback of hand movements and execution of accurate pointing.

Mean regional cerebral blood flow images of normal subjects using technetium-99m-HMPAO by automated image registration.

UNLABELLED: The purpose of this study was twofold: to calculate relative uptake values for 99mTc-HMPAO in various regions of the normal brain after alignment and registration to a standard shape and size, and to validate the automated image registration (AIR) program for SPECT-to-SPECT transformation. METHODS: Thirty subjects took part in this study. Technetium-99m-HMPAO brain SPECT and x-ray-CT scans were acquired. SPECT images were normalized to an average activity of 100 counts/pixel. Intersubject accuracy was evaluated on brain images of 17 normal subjects (mean age = 64.9 +/- 8.7 yr). These images were aligned and registered to a standard size and shape with the help of AIR. Realigned images were overlaid on reference images to determine the overlap areas. Intrasubject accuracy was evaluated by realigning 20 degree rotated brain images with an index calculated as: overlap area/(overlap area + nonoverlap area). Anatomical variability between realigned target and reference images was evaluated by measurements on corresponding x-ray-CT scans, realigned using transformations that were established by the SPECT images. Realigned brain SPECT images of 30 normal subjects (mean age = 50.7 +/- 18.7 yr), including those subjects examined in the accuracy validation study, were used to generate mean and s.d. images. Images based on the mean value of each voxel (n = 30) were compared with other mean images prepared by the human brain atlas (HBA) standardization technique on a voxel-by-voxel basis to generate T maps. RESULTS: Accuracy indices were 0.98 +/- 0.006 and 0.99 +/- 0.002 for the intersubject and intrasubject evaluations, respectively. The maximum anatomical variability was 4.7 mm after realignment. Paired Student's t-test comparisons of mean HBA and AIR images revealed statistically significant differences for the deep white matter, pons and occipito-temporal regions. These differences could be explained by variation in the population being studied and the protocol for data handling by AIR and HBA. CONCLUSION: AIR aligns and registers brain SPECT images with acceptable accuracy, without the necessity of MRI or x-ray-CT scans.

SPECT imaging of normal subjects with technetium-99m-HMPAO and technetium-99m-ECD.

UNLABELLED: Technetium-99m-HMPAO and 99mTc-ECD have been used for regional cerebral blood flow (rCBF) studies using SPECT. However, details of the normal perfusion patterns of these agents still remain to be clarified. HMPAO-SPECT and ECD-SPECT images of normal individuals were investigated using an anatomical standardization technique. METHODS: Twenty healthy subjects participated in this study. In 10 of these, regional cerebral perfusion was measured with HMPAO, and in the other 10, ECD was used. All SPECT images were globally normalized to 50 counts/voxel, and then, each SPECT image was transformed into a standard brain anatomy format with the aid of x-ray CT of each subject and a computerized human brain atlas system (HBA). Mean and s.d. images for each tracer were calculated on a voxel-by-voxel basis. For comparison of these SPECT images with blood flow, rCBF images were generated using PET in a separate group of 10 healthy male subjects during an eyes-closed resting state. The PET images were globally normalized to 50 ml/100 g/min and anatomically standardized using each subject's MRI and the HBA for the SPECT images. RESULTS: In the HMPAO-SPECT images, relatively high radioactivities Were observed in the basal ganglia and cerebellum. In the ECD-SPECT images, high levels were observed in the medial aspect of the occipital lobe. These regions with high radioactivity were not apparent in the rCBF-PET images. CONCLUSION: While both HMPAO and ECD have been used to investigate rCBF, their perfusion patterns differ from rCBF-PET images. This presumably reflects differences in the mechanism of accumulation of each agent in the brain. For clinical diagnoses, these patterns must be taken into consideration.

Activity in the parietal area during visuomotor learning with optical rotation.

Regional cerebral blood flow (rCBF) was measured in six subjects to study changes of activity in the parietal cortex during learning of a visually guided pointing task with a discrepancy of visuomotor coordination and to determine whether reorganization affects the parietal activity after learning. During the early stage of learning, the right posterior parietal cortex showed a significant increase in rCBF. During the late stage, on the other hand, significant activation was noted in the postcentral gyrus of the right hemisphere. These results support a role for the posterior parietal cortex in remapping visuomotor coordinates and suggest the involvement of the human postcentral gyrus in retaining sensorimotor coordinates, considered to relate to the self image of the hand.

Two different areas within the primary motor cortex of man.

The primary motor area (M1) of mammals has long been considered to be structurally and functionally homogeneous. This area corresponds to Brodmann's cytoarchitectural area 4. A few reports showing that arm and hand are doubly represented in M1 of macaque monkeys and perhaps man, and that each subarea has separate connections from somatosensory areas, have, with a few exceptions, gone largely unnoticed. Here we show that area 4 in man can be subdivided into areas '4 anterior' (4a) and '4 posterior' (4p) on the basis of both quantitative cytoarchitecture and quantitative distributions of transmitter-binding sites. We also show by positron emission tomography that two representations of the fingers exist, one in area 4a and one in area 4p. Roughness discrimination activated area 4p significantly more than a control condition of self-generated movements. We therefore suggest that the primary motor area is subdivided on the basis of anatomy, neurochemistry and function.

Activation by attention of the human reticular formation and thalamic intralaminar nuclei.

It has been known for over 45 years that electrical stimulation of the midbrain reticular formation and of the thalamic intralaminar nuclei of the brain alerts animals. However, lesions of these sectors fail to impair arousal and vigilance in some cases, making the role of the ascending activating reticular system controversial. Here, a positron emission tomographic study showed activation of the midbrain reticular formation and of thalamic intralaminar nuclei when human participants went from a relaxed awake state to an attention-demanding reaction-time task. These results confirm the role of these areas of the brain and brainstem in arousal and vigilance.

Somatosensory activations of the parietal operculum of man. A PET study.

We tested the hypothesis that somatosensory discrimination of roughness (microgeometry) but not of shape (macrogeometry) would activate the parietal operculum (PO) in man. It was also investigated whether a simple square pulse indentation of the skin on the index finger would activate the PO. Regional cerebral blood flow was measured with [15O]butanol and positron emission tomography in a total of 20 normal volunteers. Ten subjects used their right hand to discriminate objects that differed in roughness and similar smooth objects that differed in length. Ten other subjects pressed a button when they felt a square pulse indentation of the skin on their right index finger in a somatosensory reaction time task. Discrimination of roughness activated one field in the PO contralaterally and two fields ipsilaterally to the stimulated hand. The discrimination of length activated one field in the PO located ipsilaterally to the stimulated hand. The somatosensory reaction time task also activated one contralateral and two ipsilateral fields in the PO, and these fields partially overlapped the activated fields in the roughness discrimination task. Based on the extension of these fields and their overlaps we conclude that there exist at least one part of the contralateral PO and at least two parts of the ipsilateral PO that can be activated by somatosensory stimulation of the right hand. We argue further that the contralateral activated part contains a region than can be activated by roughness.

[Two cases of malignant effusion treated successfully by loco-regional administration of carboplatin].

We encountered two cases of malignant effusion treated successfully by loco-regional administration of carboplatin (CBDCA). One case was a 60-year-old male showing recurrent non-small cell lung cancer (adenocarcinoma) with pericarditis carcinomatosa. A drainage from the pericardial cavity was performed and a total dose of 600 mg (single dose, 300 mg) of CBDCA was administered into the cavity. Malignant effusion disappeared and radiographic improvement was also observed. No pericardial effusion was observed for about 4 months after the loco-regional treatment, till he died of lung cancer. Another case was a 58-year-old male having invasive thymoma (mixed cell type) with pleuritis carcinomatosa. He received palliative radiation therapy and systemic cancer chemotherapy concurrently. As a loco-regional therapy, drainage from the pleural cavity was performed, and 300 mg of CBDCA and 10 KE of OK-432 were administered into the cavity. A remarkable reduction of pleural effusion was observed after the therapy. No increase of pleural effusion has been observed radiographically for about 18 months, and the patient is still alive with the tumor. The side effects due to loco-regional administration of CBDCA were quite tolerable in both cases.