Hiroshi Uenohara

A new technology for revascularization of cerebral embolism using liquid jet impact

Revascularization time is the dominant factor in the treatment of acute cerebral embolism. In this paper we describe a rapid revascularization therapy using liquid jets generated by the interaction of gas bubbles with shock waves, which impact on the thrombi. The interaction of a shock wave with a gas bubble attached to an artificial thrombus which was inserted into a tube model of a cerebral artery was investigated. The shock wave was generated by detonating a microexplosive pellet. The overpressure of the shock wave was 3.0 +/- 0.6 MPa (n = 7) and 12.7 +/- 0.4 MPa (n = 3). The initial air bubble radii were varied from 0.87 mm to 2.18 mm. The subsequent collapse of the bubble was photographed using a high-speed framing camera, and the liquid jet penetrating into the artificial thrombus was visualized using x-ray photography. The penetration depth of the liquid jet increased with increasing bubble size. There was an optimal separation distance between the bubble and the shock wave source to obtain the maximum penetration depth. Liquid jets have the potential to penetrate through thrombi in as little as a few microseconds, and with very efficient ablation.

Initiation and propagation of lipid peroxidation in cerebral infarction models. Experimental studies.

The possibility that cerebral ischaemia or cerebral hypoxia may initiate a series of free radical reactions in brain lipid constituents was explored by measuring sequential changes in chemiluminescence (CL) and electron spin resonance (ESR) during hypoxia or ischaemia load. Brain hypoxia was induced by means of arterial hypoxaemia (PaO2 17-22 mmHg), normocapnia (PaCO2 28-38 mmHg) and normotension (MABP 100-140 mmHg). To obtain lowered PaO2, 4% O2-96% N2 mixed gas was used for artificial ventilation. Spin trapping technique was used in ESR measurement and applied to the detection of free radicals generated in the ischaemic brain homogenate of three-vessel occlusion rat model (global highly ischaemic model with basilar artery coagulation and bilateral carotid artery clipping). Chemiluminescence (CL) began to rise in hypoxic or ischaemic loading and indicates high amounts at an early period of post-hypoxic or ischaemic state. The CL spectroanalysis by wavelength showed five peaks at 480 nm, 520-530 nm, 570 nm, 620-640 nm and 680-700 nm in both hypoxic and ischaemic brain. ESR measurement revealed the PBN (phenyl-t-butyl nitrone) trapped radical, which has hyperfine splitting constants of AN = 16.2-16.5 G and AH beta = 3.6-3.8 G in ischaemia model. An analysis of sequential change of PBN adduct intensity shows a peak at 30 min of ischaemic loading and a marked increase in the recirculation period. Preservation of ATP and marked lactic acidosis were seen in the 5 min hypoxic loading, elsewhere depletion of ATP and marked lactic acidosis were seen in the 5 min, 30 min ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Innovative technology for tissue disruption by explosive-induced shock waves

We have developed a novel, less invasive, shock wave source that can be introduced into an arbitrary position in a human body percutaneously. Using this technique we can disrupt cells locally. The shock wave source consists of an explosive, an optical fiber, a balloon catheter, and a Nd:YAG laser, which generates a spherical explosive shock wave. The destructive potential of the present source for injuring tissue was confirmed and the subsequent cell elongation and split in the direction of the shock wave has been observed.

Development of a de novo arteriovenous malformation after bilateral revascularization surgery in a child with moyamoya disease

The development of a de novo arteriovenous malformation (AVM) in patients with moyamoya disease is extremely rare. A 14-year-old girl developed an AVM in the right occipital lobe during the 4-year postoperative period following successful bilateral revascularization surgeries. She suffered a transient ischemic attack with hemodynamic compromise of the bilateral hemispheres at the age of 10 years. Results of an initial examination by 1.5-T MRI and MR angiography satisfied the diagnostic criteria of moyamoya disease but failed to detect any vascular malformation. Bilateral direct and indirect revascularization surgeries in the anterior circulation relieved her symptoms, and she underwent MRI and MR angiography follow-up every year after surgery. Serial T2-weighted MRI revealed the gradual appearance of flow voids in the right occipital lobe during the follow-up period. Magnetic resonance angiography ultimately indicated the development of an AVM 4 years after these surgeries when catheter angiography confirmed the diagnosis of an AVM in the right occipital lobe. The AVM remained asymptomatic, and the patient remained free of cerebrovascular events during the time she was observed by the authors. Acquired AVM in moyamoya disease is extremely rare, with only 3 pediatric cases including the present case being reported in the literature. The development of a de novo AVM in a postoperative patient with moyamoya disease appears to be unique, and this case may provide insight into the dynamic pathology of AVMs.

Prediction of neurological recovery using apparent diffusion coefficient in cases of incomplete spinal cord injury.

BACKGROUND: Magnetic resonance imaging is useful in evaluating acute spinal cord injury. Apparent diffusion coefficient (ADC) values obtained by diffusion-weighted imaging can differentiate cytotoxic edema from vasogenic edema through microscopic motion of water protons. OBJECTIVE: To determine whether ADC values in the cervical spinal cord match neurological grades and thus predict functional recovery in patients suffering from cervical spinal cord injury. METHODS: Diffusion-weighted images were obtained using 15 axial slices covering the cervical spinal cord from 16 consecutive patients. ADC values were determined for both gray and white matter. All patients were treated surgically. Patient neurological status was evaluated preoperatively and postoperatively with the Frankel classification and neurosurgical cervical spine scale. One patient had complete spinal cord injury and showed no recovery. Using 15 patients with incomplete injury, we analyzed correlations between preoperative ADC values and neurological grading, degree of postoperative recovery, or cavity formation in follow-up magnetic resonance images. For comparison, ADC values of 11 healthy volunteers were also calculated. RESULTS: There was significant correlation between ADC values and degree of postoperative recovery (P = .02). ADC values of patients showing cavity formation were significantly lower than those of patients without cavity formation (0.70 vs 0.96 × 10−3 mm2/s; P = .01). The cutoff ADC value of 0.80 × 10−3 mm2/s resulted in 75% sensitivity and 81.8% specificity for predicting cavity formation. CONCLUSION: Low ADC values in acute spinal cord injury may indicate postoperative cavity formation in the injured spinal cord and predict poor functional recovery.

Pulsed liquid jet dissector using holmium:YAG laser--a novel neurosurgical device for brain incision without impairing vessels.

Summary¶Background. Neurosurgery has long required a method for dissecting brain tissue without damaging principal vessels and adjacent tissue, so as to prevent neurological complications after operation. In this study we constructed a prototype of such a device and used it in an attempt to resect beagle brain cortex. Method. The prototype device consisted of an optical fibre, a Y adaptor, and a nozzle whose internal exit diameter was 100 µm. Cold physiological saline (4 °C) was supplied to it at a rate of 40 ml/h. Pulsed liquid jets were ejected from the nozzle by a pulsed Holmium:YAG) (Ho:YAG) laser at an irradiation energy of 300 mJ/pulse. The profile of the liquid jet was observed with a high-speed camera while changing the distance between the optical fibre end and nozzle exit (equivalent to the standoff distance). With this device (3 Hz operation), brain dissection of anaesthetized beagles was attempted while measuring the local temperature of the target. A histological study of the incised parts was also performed. Findings. When the standoff distance was 24 mm, the liquid jet was emitted straight from the nozzle at a maximum initial velocity of 50 m/s. The brain parenchyma was cut with this device while preserving vessels larger than 200 µm in diameter and keeping the operative field clear. The local temperature rose to no more than 41 °C, below the functional heat damage threshold of brain tissue. Histological findings showed no signs of thermal tissue damage around the dissected margin. Interpretation. The Ho:YAG laser-induced liquid jet dissector can be applied to neurosurgery after incorporating some minor improvements.

The association of subventricular zone involvement at recurrence with survival after repeat surgery in patients with recurrent glioblastoma.

Surgical resection is identified as an important prognostic factor for survival in patients undergoing initial resection of glioblastoma (GBM). However, in patients with tumor recurrence, the benefits of repeat surgery remain unclear. Recent reports have stated that the association between initial surgery for GBM and subventricular zone (SVZ) influences survival. The current study examined the relationship of SVZ involvement in recurrent GBM to survival time after reoperation. We conducted a retrospective review of 61 consecutive patients who had undergone repeat surgery for recurrent GBM at our institution between 1997 and 2010. Survival after repeat surgery were compared between patients with (n = 29) and without (n = 32) SVZ involvement at recurrence using univariate analysis with known prognostic factors, including sex, age, Karnofsky Performance Status (KPS) score at recurrence, recurrent tumor size, initial SVZ involvement, and adjuvant therapy after repeat surgery, as variables. All 26 SVZ-positive tumors at initial diagnosis recurred as SVZ-positive tumors, while 32 of 35 SVZ-negative tumors at initial diagnosis remained SVZ-negative at recurrence; the remaining three were SVZ-positive at recurrence. Survival after repeat surgery was decreased in patients with recurrent GBM involving the SVZ at recurrence (p = 0.022). No other prognostic factors for survival after repeat surgery were identified in this study. This finding may have prognostic and therapeutic significance.

The protective effect of mannitol, vitamin E and gluccorticoid on ischaemic brain injury: evaluation by chemiluminescence, energy metabolism and water content

We currently have used three drugs in combination [mannitol, vitamin E and glucocorticoid (beta-methasone)] for the treatment of cerebral infarction in the acute stage. For the purpose of evaluating the efficacy of this therapy, we have conducted experiments evaluated by chemiluminescence (CL), energy metabolism and water content of the cortex using a global highly ischaemic rat brain. During the ischaemic period, CL levels increased with time and further increases were seen after recirculation of the blood flow. However, in the group which was administered the three drugs in combination, there was marked inhibition of CL value. Determination of adenine nucleotide and carbohydrate levels revealed that these drugs in combination promoted their recovery at the time of recirculation following ischaemia. In particular, the increase in lactate was inhibited during the ischaemia, thus preventing the progression of lactic acidosis. Moreover, in the group given all three drugs and in the group given 20% or isotonic mannitol, the increase in cortical water content following recirculation was inhibited. From these results it is deduced that these three drugs inhibit the cellular destruction by attenuation of free radical mediated peroxidation.

A novel method of drug delivery for fibrinolysis with Ho:YAG laser-induced liquid jet

Two of the problems inherent in the treatment of cerebral emboli are the narrow therapeutic time window and the severe side effects of fibrinolytic drugs. Thus, it is necessary to develop a new method of removing a cerebral thrombus more rapidly and with smaller quantities of fibrinolytics. The behaviour of a bubble formed by holmium (Ho):YAG laser irradiation in a capillary tube filled with pure water was observed at various stand-off distances (L; distance between the end of optical fibre and the capillary exit). Subsequently, a liquid-jet generator was created by insertion of an optical fibre (core diameter: 0.6 mm) into a catheter (6 Fr) filled with pure water, and a pulsed Ho:YAG laser (pulse duration time=350 µs, laser energy=230 mJ/pulse) was used to irradiate the optical fibre. The maximum penetration depth, into a gelatin artificial thrombus, of a liquid jet generated with this device was measured for various stand-off distances. Additionally, the phenomenon and the pressure around the catheter exit were captured via shadowgraph and PVDF needle hydrophone, respectively. The laser-induced bubble in the capillary tube grew rapidly in the direction of propagation and generated a liquid jet. The maximum penetration depth of this liquid jet into an artificial thrombus increased in proportion to L and reached a maximum value (9 mm) when L was around 13 mm. A shock wave whose overpressure at a point 4 mm away from the catheter exit exceeded 12 MPa was captured by shadowgraph. It was concluded that Ho:YAG laser irradiation within a water-filled catheter caused liquid jet formation, which could penetrate straight into an artificial thrombus. Hence, this jet is expected to promote fibrinolysis by means of injecting fibrinolytics deeply into the thrombus. After resolving some problems, this system will be applied to an endovascular therapy for cerebral embolisms in the near future.

Clinical Manifestations, Character of Aneurysms, and Surgical Results for Unruptured Cerebral Aneurysms Presenting with Ophthalmic Symptoms

OBJECTS Cases with unruptured cerebral aneurysms presenting with visual symptoms were investigated about their site, size, symptom, operative methods and results. MATERIAL Between 1984 and 1999, 8 cases were treated in Sendai National Hospital. One man and 7 women, mean age 66.4 years. Ophthalmic symptoms were as follows: diplopia in 6, visual acuity deterioration in 2, impaired visual field in 2 and ptosis in 3. Aneurysm location was IC cavernous in 3, IC ophthalmic in 3, ICPC in 1 and Acom in 1. Aneurysms of more than 25 mm numbered 6 cases. RESULTS Operative methods and results were as follows: Direct clipping 3 cases, parent artery occlusion + EC/IC bypass 4 cases, Aneurysm trapping + EC/IC bypass 1 case. One patient who underwent direct clipping died following intraoperative complication. Of the remaining 7 cases, visual symptoms were improved in 4, remained unchanged in 2 cases, worsened in 1 case. CONCLUSIONS These results suggest that in cases with unruptured large or giant aneurysms presenting with ophthalmic symptoms, especially in IC cavernous or IC ophthalmic aneurysms, parent artery occlusion + EC/IC bypass is the safest operative procedure.