Motoharu Hayakawa

Brain-specific gene expression by immortalized microglial cell-mediated gene transfer in the mammalian brain

The intra‐arterial injection of immortalized microglia transfected with the lacZ gene, resulted in the expression of β‐galactosidase in the rat brain at 48 h and the activity of β‐galactosidase was detected for up to 3 weeks post‐injection. More than 30‐fold higher activity of β‐galactosidase was detected in the brain than in the liver, lung or spleen at 48 h post‐injection. This method allows us to easily deliver the gene of interest to the brain without influencing other organs. Our brain‐targeting gene delivery system can facilitate gene therapy of several brain disorders, including brain tumor, metabolic disorders, and degenerative disorders, as well as investigation into the roles of particular genes in brain function and development.

Whole-Brain Perfusion CT Performed with a Prototype 256–Detector Row CT System: Initial Experience

PURPOSE To preliminarily evaluate the feasibility and potential diagnostic utility of whole-brain perfusion computed tomography (CT) performed with a prototype 256-detector row CT system over an extended range covering the entire brain to assess ischemic cerebrovascular disease. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Eleven cases in 10 subjects (six men, four women; mean age, 64.3 years) with intra- or extracranial stenosis were retrospectively evaluated with whole-brain perfusion CT. Three readers independently evaluated perfusion CT data. The diagnostic performance of perfusion CT was visually evaluated with a three-point scale used to assess three factors. Differences between four axial perfusion CT images obtained at the basal ganglia level (hereafter, four-section images) and whole-brain perfusion CT images were assessed with the paired t test. In four subjects, the interval between perfusion CT and single photon emission computed tomography (SPECT) was 1-17 days (mean, 10.3 days). Correlation between perfusion CT findings and SPECT findings was assessed with the Spearman correlation coefficient. RESULTS Three-dimensional perfusion CT images and axial, coronal, and sagittal whole-brain perfusion CT images were displayed, and the extent of ischemia was assessed. Mean visual evaluation scores were significantly higher for whole-brain images than for four-section images (4.27 +/- 0.76 [standard deviation] vs 2.55 +/- 0.87). The cerebral blood flow ratios of the ischemic lesions relative to normal regions scanned with perfusion CT (x) and SPECT (y) showed a significant positive correlation (R(2) = 0.76, y = 0.44 x + 0.37, P < .001). CONCLUSION Perfusion CT performed with a 256-detector row CT system can be used to assess the entire brain with administration of one contrast medium bolus. Thus, ischemic regions can be identified with one examination, which has the potential to improve diagnostic utility.

Multi-slice 3D-CTA - an improvement over single slice helical CTA for cerebral aneurysms.

Summary.Summary. Background and Objective: The aim of this study was to demonstrate the utility of volume rendered multi-slice helical three-dimensional CT angiography in patients with cerebral aneurysm when compared with single slice CT angiography and formal digital subtraction angiography. Methods: A prototype Toshiba Aquilon multi-slice CT scanner was employed with the following scan conditions: voltage 135 kV; current 300 mA; slice thickness 0.8 mm; scan speed 0.75 sec/cycle; couch speed 1 mm/sec; range 50 mm from foramen magnum; scan pitch 3; three dimensional images were reconstructed using multiple image projections and integral volume rendering algorithms on a Xlink/Xtension workstation. 80 cases of multi-slice CTA for cerebral aneurysm carried out at Fujita University from January 1999 to January 2001 were reviewed. Results: The advantages of multi-slice imaging are illustrated with representative cases of cerebral aneurysm – good demonstration of three dimensional anatomy, appreciation of perforators down to 1 mm in size, delineation of the vessels around the aneurysm complex, relationship between the aneurysm and skull base, information on calcification, thrombus and blebs in the wall and eleven routine views for perusal. Conclusion: Multi-slice CTA is a significant improvement over single slice CTA for cerebral aneurysms. It is our experience the superior and precise images produced by multi-slice technology displays anatomical information not readily available from standard DSA. Multislice 3D-CTA is relatively non-invasive and provides better and adequate detail for surgical planning. The basis of multi-slice CT angiography is described. Multi slice CTA is changing the way cerebral aneurysms are being managed nowadays. New advances in the technology of multi-slice CTA resulting in increased image resolution are outlined.

Application of three-dimensional CT angiography (3D-CTA) to cerebral aneurysms.

BACKGROUND 3D CT angiography (3D-CTA) is a noninvasive imaging modality for cerebral aneurysms. 3D-CTA is helpful in the evaluation of the configuration of the aneurysm, the surrounding vessels, and the inside of the aneurysm dome. Clinical application of this technique in complicated large cerebral aneurysms showed that with 3D-CT endoscopic imaging, anatomical details of cerebral aneurysms such as the orifice of the aneurysm, intraluminal thrombus, and calcification of the wall could be clearly demonstrated. Using the 3D-imaging method with helical CT, virtual views of various surgical approaches can be compared preoperatively. This information was found to be very useful for determining difficult aneurysms for coil embolization or direct surgery including complicated and broad-based aneurysms. METHODS Helical CT scanners (TOSHIBA X-vigor) are used for intracranial vascular lesions. At present, nearly stereoscopic images at a pixel size of 0.35 x 0.35 x 0.4 mm are obtained by reconstruction under the following conditions: slice thickness, 0.8 mm; couch top speed, 1.0 mm/ sec.; 130 kV; 220 mA; visual field, 18 cm in diameter (11 cm after extension); pitch, 0.4 mm; and opposed beam interpolation. RESULTS AND CLINICAL APPLICATION: By virtual vascular 3D-CT endoscopy, the lumen of the cerebral aneurysm is displayed by the surface rendering method. Its clinical applications include 1) Demonstration of three-dimensional aneurysm morphology, including the dome and the neck region; 2) Preoperative simulation; 3) Confirmation of parent blood vessels flowing into and out of aneurysms and visualization of aneurysmal lumen calcification. Coronal and sagittal sections can demonstrate whether the branches arise from the aneurysm or aneurysmal neck. The limitation of 3D-CTA is in delineating perforating arteries that are less than 1.2 mm in diameter. The problem with virtual vascular 3D-CT endoscopic images is that endoscopic findings in the vascular wall are incomplete because of the partial volume effect and pulsation of the aneurysm and vascular wall. CONCLUSIONS Helical Scanning-CT (HES-CT) is an excellent noninvasive diagnostic modality for cerebral aneurysm detection. 3D-CT angiography has distinct advantages in evaluating aneurysms and selecting the most appropriate therapeutic modality.

Migration activity of microglia and macrophages into rat brain

We examined the entry of intra-arterially injected microglia and macrophages into the brain using a rat muscle graft model to compare their respective abilities to invade the brain parenchyma. Isolated microglia without any activation treatment entered into the brain with or without the muscle graft, while macrophages activated by phorbol 12-myristate-13-acetate (PMA) entered the brain only in the presence of the muscle graft. These results suggest that microglia have a higher affinity for the brain than macrophages.

Can 3D-CTA Surpass DSA in Diagnosis of Cerebral Aneurysm?

Summary After introducing of Helical scanning CT (HCT) and 3D-CTA (three-dimensional CT angiography), various improvements to these methods have been made every year to achieve better imaging quality. The current resolution permits visualisation of the internal structure of tumors, although as yet insufficiently clearly. We suggest that these improvements can be more efficient than conventional cerebral aneurysms angiography. In this study, we compared HCT and 3D-CTA with conventional cerebral angiography in patients with cerebral aneurysms at our facility. We also examined whether 3D-CTA has the possibility of independent clinical application and can surpass conventional DSA in diagnostic efficacy. In this paper, we found this information insufficient in clipping operations using 3D-CTA only when 1) It was difficult to distinguish a crooked infundibular dilation from an aneurysm, 2) Imaging threshold influenced the measured value of the vascular diameter and 3) It was also difficult to confirm whether the peripheral vessels adhere to the aneurysm. In conclusion, from the result of the comparison between 3D-CTA and DSA in this study, it was concluded that 3D-CTA is a reliable alternative method to conventional angiography in the diagnosis of anterior circulation and most aneurysms of regular size. In such cases it may be possible to obtain the same quality of preoperative information, but it is less invasive.

Detection of pulsation in ruptured and unruptured cerebral aneurysms by electrocardiographically gated 3-dimensional computed tomographic angiography with a 320-row area detector computed tomography and evaluation of its clinical usefulness.

BACKGROUND:In ruptured cerebral aneurysms (RCAs), identification of the rupture point of a cerebral aneurysm is useful for treatment planning. In unruptured cerebral aneurysms (URCAs), detection of the risk of aneurysmal rupture is also useful for patient management. OBJECTIVE:Electrocardiographic (ECG)-gated 3D-CT angiography was performed for patients with RCAs and URCAs using 320-row area detector CT (ADCT) to detect pulsation of the cerebral aneurysms. The clinical usefulness of this method was then evaluated. METHODS:Twelve patients had 12 RCAs, and 39 patients had 53 URCAs. A 320-row ADCT system was used to scan. ECG-gated reconstruction was then performed with the R-R interval divided into 20 phases. RESULTS:Pulsation was observed in 10 of the 12 RCAs. The bleeding site was considered to correspond to the area of pulsation. Pulsation was observed in 14 of 53 URCAs. Thirteen patients with 18 URCAs were followed. Of the 11 URCAs in which pulsation was not observed, 1 showed a change in shape. Of the 7 URCAs in which pulsation was observed, 3 showed a change in shape. URCAs in which pulsation was observed were more likely to show a change in shape (P = .082). CONCLUSION:The area of pulsation was found to correspond to the bleeding site in many RCAs. This information would be extremely useful for treatment planning. The detection of pulsation in an URCA is therefore considered to provide useful information for patient management.

Treatment of a spontaneous intracranial dissecting aneurysm with stent-assisted coil embolization

Arterial dissection is now recognized as an important cause of stroke. Most reported dissections involve the extracranial portion of the internal carotid artery (ICA) and vertebral arteries. Spontaneous dissecting aneurysms of the intracranial ICA are uncommon. Endovascular treatment for cerebral aneurysms has become widespread; however, the dissecting aneurysm is still difficult to treat if the parent artery has to be preserved. More recently, stenting has been advocated for use with endosaccular coiling, with the coils held in place by the stent. We herein report a spontaneous intracranial ICA dissecting aneurysm in a 51-year-old woman who was treated using a new technique of combined stent and coils.

Management of Complex, Surgically Intractable Intracranial Aneurysms: The Option for Intentional Reconstruction of Aneurysm Neck Followed by Endovascular Coiling

Background: A limited series of patients with aneurysm were reviewed retrospectively to analyze strategies for integrating microsurgical and endovascular techniques in the management of complex, surgically intractable aneurysms. Methods: Four patients were managed in Fujita Health University with a multimodality approach: intentional reconstruction of the aneurysm neck followed by endovascular coiling. Results: A total of 5 aneurysms were treated, of which 3 were large or giant in size, and 3 were fusiform or multilobulated. Complete angiographic obliteration was confirmed in 4 aneurysms (80%). All patients had a good outcome (Glasgow Outcome Scale score 5; mean follow-up, 64 months). Conclusion: As for complex, surgically intractable aneurysms, the intentional reconstruction of the aneurysm neck followed by endovascular coiling should be considered more often.

Comparison of cerebral aneurysm volumes as determined by digitally measured 3D rotational angiography and approximation from three diameters.

This study compared digital measurement of aneurysm volume by 3D rotational angiography (3D-RA) with an approximation technique using three diameters of an aneurysm to re-interpret previously reported optimal packing densities (volume embolization ratio, VER) in coil embolization of intracranial aneurysms. Estimation of the volume of saccular aneurysms is important for calculation of the VER, which is in turn reported to be useful for prediction of coil compaction. The conventional formula for the volume estimation is V=4/3 π(A/2) (B/2) (C/2), where A, B, and C are the aneurysmal height, length, and width measured on 3D-RA image respectively. Using 3D rotational angiography data from 74 aneurysms, the approximated volume generated using the conventional formula was directly compared with the digitally measured volume. The digitally measured volume varied from 0.003 ml to 7.935 ml, and the dome-to-neck ratio (D/N) from 0.79 up to 4.62. We found that the conventional formula almost systematically underestimated the volume by up to 50 %, particularly when the neck was large relative to the dome (D/N<2). On average, digitally measured volume was 1.26!1.29 times larger than the approximated volume obtained using the conventional formula. Conventional 2D angiography based aneurysm volume calculation tends to underestimate an aneurysm volume, so the so-called VER (volume embolization ratio) could be overestimated.