Fully automatic rapid DNA Ploidy Analyzer for intraoperative rapid diagnosis support.

Frozen section studies are a useful method to rapidly define tumor malignancy and identify the extent of surgical resection. However, diagnosis with a frozen section is qualitative and sometimes difficult. Therefore a quantitative method for grading tumors is desired. We have already reported a technique of intraoperative flow cytometry (iFC) that supports intraoperative histopathological examination of frozen sections. In this study, we report an advanced system named "Fully Automatic Rapid DNA Ploidy Analyzer" with a tissue pretreatment function and a freeze-dried reagent kit for cell staining. To evaluate our system, we analyzed samples from glioma patients who underwent open surgery for brain tumors. We observed obvious difference of the Malignancy Index (MI) between neoplastic and perilesional brain tissue (26.0 ±22.1% and 4.1 ±2.5%, respectively, P<0.001). Cut-off level for identification of the tumor in the biopsy specimen was 6.8% which provided 86% sensitivity and 81% specificity. We also obtained a good correlation between the MI and histological grade (WHO grading). Our new system also enabled finishing the process from sample preparation to the end of analysis in ten minutes or less. These results demonstrate that our fully automatic rapid DNA ploidy analyzer is feasible for rapid determination of glioma presence in a surgical biopsy sample.

A surgical navigation system for aortic vascular surgery: a practical approach.

In aortic vascular surgery, a navigation system must represent the anatomical map of individual patient in order to detect the important artery. To provide a proper fit for positions along the dorsoventral axis, the spinous process was added to a currently used anatomical point set consisting of four anterior body landmarks. In addition, we attempted to reduce the registration error by compensating for alignment errors resulting from variations in tissue thickness at each landmark. The alignment values were examined using a human phantom consisting of a skeleton model with subcutaneous tissue in the semilateral position. Using this method, a phantom simulation and five clinical trials were performed. Target errors were evaluated at the orifice of the intercostal artery. In the phantom simulation, the error at the target point was 4.1 ± 2.7 mm. However, for one patient undergoing thoracoabdominal aortic aneurysm replacement surgery, the target error was 8.0 mm using the proposed method.

11C-methionine uptake correlates with combined 1p and 19q loss of heterozygosity in oligodendroglial tumors.

BACKGROUND AND PURPOSE: Oligodendroglial tumors with 1p/19q LOH are known to show longer patient survival than those without 1p/19q LOH, but the reason for this clinical difference has not been elucidated, to our knowledge. This study was designed to clarify whether uptake of MET correlates with 1p/19q LOH of oligodendroglial tumors. MATERIALS AND METHODS: This study included 102 consecutive patients with supratentorial WHO grade II and III oligodendroglial tumors (39 oligoastrocytic and 63 oligodendroglial tumors) that were resected and diagnosed between January 2008 and August 2011 at Tokyo Women's Medical University Hospital. These patients underwent MET PET T/N ratio measurement before treatment. T/N ratios were calculated by dividing the maximum SUV for the tumor by the mean SUV of the contralateral normal frontal cortex. After surgery, FISH for resected tissues was used to determine 1p/19q LOH. RESULTS: The mean T/N ratio of tumors with 1p/19q LOH was significantly greater than that of tumors without 1p/19q LOH (P = .0166). The threshold T/N ratio value of 2.46 was found to correlate significantly with 1p/19q LOH by univariate (P = .0011) and multivariate analyses (P = .0209) in all tumors. CONCLUSIONS: The T/N ratio on MET PET might be a useful aid to the diagnosis of 1p/19q LOH. Our data add new information on the biology and imaging characteristics of oligodendroglial tumors with 1p/19q LOH.

"Donut's shape" radiosurgical treatment planning for large cystic metastatic brain tumors.

BACKGROUND: Radiosurgical management of large cystic metastatic brain tumors represents a significant challenge. Nevertheless, modified dose planning has shown beneficial results in such cases. METHOD AND RESULTS: "Donut's shape" radiosurgical treatment planning is based on the chain-like application of multiple, small-sized isocenters for selective coverage of the contrast-enhancing tumor capsule and minimal irradiation of the central cystic area. Such an approach was used for the management of large cystic intracranial metastases, which were not accompanied by a significant mass effect and did not require immediate volume reduction. Treatment was done using Leksell Gamma Knife model C with automatic positioning system. The majority of treated lesions showed significant shrinkage after radiosurgery and no major complications were met. CONCLUSION: Large cystic metastatic brain tumors may be successfully treated with gamma knife radiosurgery alone using the proposed "donut's shape" dose planning with coverage of the contrast-enhancing tumor capsule by multiple small-sized isocenters.

Objective skill analysis and assessment in neurosurgery by using an ultra-miniaturized inertial measurement unit WB-3--pilot tests.

In recent years there has been an ever increasing amount of research and development of technologies and methods to improve the quality and the performance of advanced surgery. In several fields, such as laparoscopy, various training methods and metrics have been proposed, both to improve the surgeon's abilities and also to assess her/his skills. For neurosurgery, however, the extremely small movements and target operating space involved have prevented until now the development of similar methodologies and systems. In this paper we present the development of an ultra-miniaturized Inertial Measurement Unit (IMU) and its application for neurosurgery skill assessment in a simple pick and place scenario. This analysis is a preliminary yet fundamental step to realize a better training/evaluation system for neurosurgeons, and to objectively evaluate and understand how the neurosurgery is performed.

Development of an articulating ultrasonically activated device for laparoscopic surgery.

BACKGROUND: Ultrasonically activated devices (USADs) offer excellent coagulating dissection performance and are broadly used, particularly in endoscopic operations. Traditional USADs, however, have fixed linear shape and are thus limited in the directions from which organs can be approached. We have developed a small USAD transducer attached to the tip of an articulating device, offering a new kind of USAD in which the tip can bend as desired. We describe herein an evaluation of the coagulating dissection performance of this new articulating USAD and an in vivo confirmation of clinical usefulness. METHODS: To evaluate coagulating dissection performance, we compared coagulating shearing on porcine splenic arteries between the articulating USAD and a Harmonic Scalpel II (HSII), representing a traditional USAD. Changing the amplitude of vibration between 60 microm and 80 microm and grip force among 1, 2, and 3 N, we measured the time required for division and bursting pressure of coagulating dissection. An in vivo experiment in a pig was also used to confirm the usefulness of the articulating USAD in laparoscopic operations. RESULTS: Division time did not differ significantly between the articulating USAD and HSII with an 80-microm amplitude of vibration and a grip force of 2 or 3 N. Bursting pressure of blood vessels showed no significant difference between articulating USAD and HSII under all experimental conditions. In the in vivo experiment, the new bendable tip of the articulating USAD displayed coagulating dissection performance equivalent to that of the traditional USAD. CONCLUSIONS: We have developed a new articulating USAD that can broaden the range of methods and approaches available for USADs and improve usefulness and safety.

Risk factors for regrowth of intracranial meningiomas after gamma knife radiosurgery: importance of the histopathological grade and MIB-1 index.

INTRODUCTION: The influence of histopathological grade and MIB-1 index of intracranial meningioma on the results of its radiosurgical management is not clear. The objective of the present retrospective study was to make an evaluation of these factors along with an analysis of other variables associated with progression-free survival after gamma knife radiosurgery (GKR). PATIENTS AND METHODS: Thirty-four intracranial meningiomas with known detailed histopathological diagnosis were analyzed. Tumors of WHO histopathological grades I, II, and III were diagnosed in 24, 3, and 7 cases, respectively. The median MIB-1 index was 1.3% (range: 0-31.9%). In 14 cases the MIB-1 index was 3.0% and more. In 26 cases the treatment was done at the time of tumor recurrence. Median volume of the neoplasm at the time of GKR was 4.1 mL (range: 0.4-43.1 mL). Median marginal dose was 12 Gy (range: 8-19 Gy). Median length of follow-up constituted 63 months (range: 19-132 months). RESULTS: Actuarial progression-free survival at 1, 3, 5, and 10 years constituted 100, 94, 83, and 58%, respectively. Histopathological grade II or III (p<0.0001), MIB-1 index 3% and more (p=0.0004), and non-skull base location (p=0.0026) of the tumor showed negative associations with progression-free survival in multivariate analyses. Actuarial progression-free survival at 5 years after GKR for benign and non-benign meningiomas constituted 100 and 45%, respectively (p<0.0001). CONCLUSION: Radiosurgery is a highly effective management option for benign intracranial meningiomas, but growth control of non-benign ones is significantly worse. It requires close neuroradiological follow-up and necessitates the search for modified treatment strategies.

Identification of the pyramidal tract by neuronavigation based on intraoperative diffusion-weighted imaging combined with subcortical stimulation.

BACKGROUND/AIMS: To identify the pyramidal tract by neuronavigation based on intraoperative diffusion-weighted imaging (iDWI) combined with subcortical stimulation. METHODS: Seven patients with brain tumors near the deep white matter underwent resection surgery using neuronavigation based on iDWI to visualize white matter bundles. Subcortical electrical stimulation was performed and electromyography was measured at the extremities when surgical manipulation came near the position corresponding to the depicted bundle. We validated the bundle depicted on iDWI by considering the responses to subcortical stimulation and the distance between the stimulation site and the depicted bundle. RESULTS: Positive motor-evoked potentials were detected in 5 of 7 patients (8 stimulations) and the distance from the stimulation site to the depicted bundle was 0-4.7 mm (mean +/- SD, 1.4 +/- 2.1 mm). Negative (no) responses were obtained in all patients when the distance was more than 5 mm. The neuronavigation system had an average error of 0.79 +/- 0.25 mm and a maximum error of 2.0 mm (n = 16). CONCLUSION: Neuronavigation based on iDWI combined with subcortical stimulation allowed surgeons to identify the pyramidal tract and avoid inadvertent injury. Our findings demonstrate that the white matter bundles depicted by iDWI can contain the pyramidal tract.

Dynamics of metabolic changes in intracranial metastases and distant normal-appearing brain tissue after stereotactic radiosurgery: a serial proton magnetic resonance spectroscopy study.

The present study evaluated the dynamics of metabolic changes in intracranial metastases and distant normal-appearing brain after stereotactic radiosurgery (SRS). Forty neoplasms were evaluated with single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) both before and after treatment. From one to six examinations (median, 3) were done in each individual case during follow-up. At the time of each investigation additional (1)H-MRS was obtained from the normal-appearing brain distant from the radiosurgical target. Investigated metabolites included N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine (Cr), and mobile lipids (Lip). Within the first month after SRS responded tumors showed a statistically significant increase in NAA/Cho ratio, and decrease of Cho content and Lip-to-normal brain Cr (nCr) ratio. By contrast, statistically significant metabolic alterations were not detected in stabilized tumors. Statistically significant volumetric and metabolic changes were not marked between three and 12 months after treatment in non-progressing lesions. Alternatively, decrease of NAA/Cho ratio, NAA content and Cr content, and increase in Lip/nCr ratio and Cho content were evident in progressive neoplasms, and subtle metabolic alterations could be revealed even before the increase in the lesion volume. Metabolic characteristics of normal-appearing brain distant from the radiosurgical target did not show statistically significant changes within the first year after treatment. In conclusion, additional use of serial (1)H-MRS during follow-up after SRS for intracranial metastases permits detailed evaluation of the metabolic tumor response and may be potentially helpful for early prediction of recurrence.

Low-grade glioma on stereotactic biopsy: how often is the diagnosis accurate?

The objective of the present study was an evaluation of the incidence and risk factors for erroneous histopathological diagnosis of low-grade glioma after stereotactic biopsy. Twenty-eight tumors diagnosed as low-grade glioma after stereotactic biopsy and surgically resected thereafter were analyzed. There were 13 astrocytomas, 7 oligodendrogliomas, and 8 mixed gliomas. All neoplasms had a lobar location. Seven tumors had contrast enhancement on MRI. The number of tissue samples obtained during stereotactic biopsy was one in 19 cases, two in 4, and three or more in 5. Complete diagnostic agreement in tumor typing and grading after stereotactic biopsy and surgical resection was attained in 10 cases (36%). Agreement in tumor typing was marked in 16 cases (57%). Erroneous typing was more frequent in tumors with an MIB-1 index of less than 3% (P = 0.0629) and mixed gliomas (P = 0.0801). Overgrading of WHO grade I tumors was marked in 3 cases (11%) and undergrading of WHO grade III gliomas in 8 cases (28%). Tumor undergrading was more frequent in cases with an MIB-1 index of more than 3% (P = 0.0045). The MIB-1 index detected after stereotactic biopsy was nearly always lower compared with those established after surgical resection (P < 0.0001). In conclusion, the histopathological diagnosis of low-grade glioma established after stereotactic biopsy is associated with a substantial risk of inaccuracy. Tumors with low proliferative activity and mixed gliomas are especially susceptible for erroneous tumor typing. Undergrading of high-grade gliomas may be suspected if the MIB-1 index in the tumor specimen constitutes more, than 3%.

Advanced computer-aided intraoperative technologies for information-guided surgical management of gliomas: Tokyo Women's Medical University experience.

The availability of the intraoperative MRI and real-time neuronavigation has dramatically changed the principles of surgery for gliomas. Current intraoperative computer-aided technologies permit perfect localization of the neoplasm, precise estimation of its volume, and clear definition of its interrelationships with the eloquent brain structures. This allows maximal tumor resection with minimal risk of postoperative disabilities. Under such conditions the medical treatment has become significantly dependent on the quality of the provided information and can be designated as information-guided management. Therefore, appropriate management of the wide spectrum of the intraoperative medical data and its adequate distribution between members of the surgical team for facilitation of the clinical decision-making is very important for attainment of the best possible outcome. Further progress in advanced neurovisualization, robotics, and comprehensive medical information technology has a great potential to increase the safety of the neurosurgical procedures for parenchymal brain tumors in the eloquent brain areas.

Ossified frontosphenoorbital meningioma en plaque, mimicking extensive hyperostosis.

Small intratumoral calcifications are often seen within meningioma, but ossification of the whole neoplasm is very rare. The case of an ossified frontosphenoorbital meningioma en plaque is presented. The radiological appearance resembled extensive hyperostosis extending from the anterior clinoid process to the cerebral convexity and falx cerebri. It is possible that, in some cases of meningioma, the identified "hyperostosis" represents partial ossification of the tumor itself.

Low-dose gamma knife radiosurgery for cavernous sinus hemangioma: report of 3 cases and literature review.

Optimal management of cavernous sinus hemangiomas remains unclear. Total microsurgical removal of these neoplasms may be extremely difficult due to their rich vascularization. Three cases of cavernous sinus hemangioma treated with low-dose Gamma Knife radiosurgery are presented. Marginal dose varied from 10 to 13 Gy. Treatment planning and radiation dosimetry were done with a goal of conformal and selective coverage of the lesion with 50% prescription isodose line using multiisocenter technique. In all cases significant shrinkage of the neoplasm was marked at 3 months after treatment. Mean volume reduction at 12 months after radiosurgery was 60% (range: 45-75%). In all patients the shrinkage of the neoplasm was accompanied by notable improvement of the preexistent oculomotor nerve palsy. No radiosurgery-related complications were met during follow-up. In conclusion, low-dose Gamma Knife radiosurgery seems to be very effective for management of cavernous sinus hemangiomas, and can be considered as a treatment modality of choice for these lesions.

E-cadherin expression in the subepithelial nevus cells of the giant congenital nevocellular nevi (GCNN) correlates with their migration ability in vitro.

BACKGROUND: Giant congenital nevocellular nevi (GCNN) are histologically characterized by the broad distribution of nevus cells in the epidermis and dermis. OBJECTIVE: To characterize E-cadherin in GCNN and define its role in nevic cell migrations. METHODS: Twenty-four cases were immunohistochemically examined and in five cases cells were isolated for primary culture for migration assays. RESULTS: The nevus cells in the superficial region showed the immunoreactivity of E-cadherin in a membranous pattern, but those in the deep part of dermis had little immunoreactivity. Ultra-structural analysis of the superficial nevus cells revealed that E-cadherin immunodeposits in the fibrillar processes around the cell body in a spotted pattern. This distribution pattern is quite different from that in the adherens junction of skin squamous epithelial cells. Boyden chamber experiments were performed using primary cultures of intradermal nevus cells. EDTA pretreatment reduced cell migration to the E-cadherin positive side when the E-cadherin positive population was relatively large in the primary cultures. CONCLUSIONS: These results indicate that E-cadherin in the nevus cells may affect nevus cell motility rather than intercellular attachment.

Differentiation of High-Grade and Low-Grade Gliomas Using Pattern Analysis of Long-Echo Single-Voxel Proton Magnetic Resonance Spectroscopy ((1)H-MRS).

The usefulness of proton magnetic resonance spectroscopy ((1)H-MRS) for glioma grading is not clear, particularly due to the absence of standard criteria for data analysis. Previously we had developed an original classification of the pathological (1)H-MRS spectra based on the identification of the predominant metabolite peak, N-acetylaspartate (NAA) for Type I, choline-containing compounds (Cho) for Type II, and mobile lipids (Lip) for Type III, and presence or absence of other metabolite peaks: lactate (Lac), Lip, or Cho. The present study evaluated the effectiveness of this classification in grading of previously non-treated gliomas. A total of 38 low-grade and 33 high-grade neoplasms were investigated. Four tumors had (1)H-MRS spectra Type I, and all of those were low-grade. Three tumors had (1)H-MRS spectra Type III, and all those were glioblastomas. Fifteen tumors with (1)H-MRS spectra Type II had a Lip/NAA ratio more than 1 (Type II C with moderate elevation of lipids), and 12 of those neoplasms were high-grade. The differences in distribution of high-grade and low-grade gliomas among another 49 gliomas with (1)H-MRS spectra Type II did not depend on the presence of Lac and/or Lip peaks, and in this subgroup NAA/Cho ratio was also evaluated. Inclusion of both characteristics (type of the (1)H-MRS spectrum and NAA/Cho ratio with defined cut-off level of 0.6) into the diagnostic algorithm yielded 72% diagnostic accuracy (95% confidence interval: 62%-82%) in discriminating high-grade and low-grade neoplasms. In conclusion, pattern analysis of the pathological (1)H-MRS spectra using the proposed classification along with evaluation of NAA/Cho ratio might be helpful for non-invasive glioma grading.

Comparison of polymerase chain reaction methods for the detection of Theileria equi infection using whole blood compared with pre-extracted DNA samples as PCR templates.

Rapid, efficient, and reproducible procedures for isolating DNA before PCR gene amplification are essential for the diagnosis of piroplasms. In this study, we evaluated the ease and reliability of detecting Theileria equi by PCR using pre-extracted DNA samples (by QIAamp DNA Mini Kit and phenol-chloroform methods) compared with blood spotted on FTA cards as PCR templates. Although minimal variations in limit of detection were observed among the methods compared, overall, the use of pre-extracted DNA samples and blood spotted on FTA cards had comparable detection limits. These results indicate that T. equi infection can be efficiently detected directly from FTA cards by PCR without the need for pre-extraction of DNA from blood samples.

Metabolic characteristics of intracranial metastases, detected by single-voxel proton magnetic resonance spectroscopy, are seemingly not predictive for tumor response to gamma knife radiosurgery.

Metabolic characteristics of intracranial metastases, detected with proton magnetic resonance spectroscopy (1H-MRS) have known associations with clinical predictors of tumor response to radiosurgery. Therefore, it can be suspected that the metabolic profile of the neoplasm by itself might have some prognostic significance for the outcome after irradiation. Twenty-six intracranial metastases, which underwent metabolic evaluation with single-voxel 1H-MRS before gamma knife radiosurgery (GKR) and were followed for at least 3 months after treatment, were selected for retrospective analysis. The tumors most frequently originated from the lungs (9 cases), breast (7 cases), colon and rectum (5 cases). The average volume of the investigated intracranial neoplasm was 5.4+/-2.0 mL. The average marginal irradiation dose was 18.6+/-2.3 Gy. The mean follow-up after GKR constituted 8.0+/-5.5 months. Tumor response to GKR was identified in 13 cases on average 2.2+/-1.8 months after treatment. Local recurrence was marked in 10 cases on average 8.7+/-4.1 months after treatment. None of the investigated 1H-MRS metabolic parameters of intracranial metastases showed a statistically significant association with the outcome after GKR. The negative results of the present study make doubtful the predictive value of metabolic characteristics of intracranial metastases, detected with single-voxel 1H-MRS, for the outcome after radiosurgery.

Usefulness of intraoperative magnetic resonance imaging for glioma surgery.

BACKGROUND: Radical resection of gliomas can increase patient's survival. There is known concern, however, that aggressive tumour removal can result in neurological morbidity. The objective of the present study was to evaluate the usefulness of low magnetic field strength (0.3 Tesla) open intraoperative magnetic resonance imaging (iMRI) for complete resection of glioma with emphasis on functional outcome. METHODS: From 2000 to 2004, 96 patients with intracranial gliomas underwent tumour resection with the use of iMRI in Tokyo Women's Medical University. There were 50 men and 46 women; mean age was 39 years. Tumour volume varied from 1.2 ml to 198 ml (median: 36.5 mL). Resection rate and postoperative neurological status were compared between control group (46 cases, operated on during the initial period after installation of iMRI), and study group (50 most recent cases, in whom surgery was done using established treatment algorithm and improved image quality). FINDINGS: Overall, mean resection rate was 93%, and medial residual tumour volume was 0.17 ml. Total tumour removal was achieved in 44 cases (46%). Compared to control group, resection rate in the study group was significantly higher (91%, vs. 95%; P < 0.05), whereas residual tumour volume was significantly smaller (1.7 mL vs. 0.025 mL; P < 0.001). Nine patients in the control group (20%) and 24 in the study group (48%) experienced temporary postoperative neurological deterioration (P < 0.01), however, the rate of permanent morbidity evaluated 3 months after surgery did not differ significantly between the groups investigated (13% vs. 14%). CONCLUSIONS: Use of iMRI during surgery for intracranial gliomas permits to attain aggressive tumour resection with good functional outcome. Nevertheless, surgical experience with the iMRI system, establishment of treatment algorithm, and improvement of image quality are of paramount importance for optimal results.

Financial management of Kashima Rinkai Specified Sewage Works.

The Kashima Rinkai Specified Sewage Works (KRSSW) is located at the northern side of the Kashima Coastal Industrial Zone, facing the Sea of Kashimanada (Pacific Ocean). It straddles one city and two townships: the city of Kashima, which boasts Kashima Port, a transportation center that was constructed on Kashimanada Beach by digging into the virgin sands, and the towns of Kamisu and Hasaki. The industries located there include steel, petrochemicals, chemicals, foodstuffs, livestock feeds, electric power and machinery metals. Industrial wastewaters with public sewage, except steel industry, are treated by the Fukashiba Treatment Plant which is managed by the Ibaraki Prefectural Government. The financial management of KRSSW is analysed to show its stand-alone condition.

Damper design for improving S/N ratio of the seismocardiogram monitoring in the OpenMRI-guided operating theater.

The final goal of this study is to establish a method of measuring precisely the seismocardiogram (SCG) of a patient who lying in an open magnetic resonance imaging (openMRI) machine for myocardial ischemia monitoring during surgery. Vibration isolation from the gantry vibration during MRI scan is essential for clinical use. Authors previously reported the comparison between the SCG and the gantry vibration. A damper to decrease vibration below 30 Hz should be designed. In this paper, authors fabricated a damper model to check the feasibility of the damping effect, and compared with the patient bed mat. Experiment using a vibrator showed 1) the viscosity damping coefficient of the current damper was 2 kN s/m, 2) owing to the damper, peak ratio between input and output amplitude decreased from 2.5 to 1.2, and 3) natural frequency decreased from 12 Hz to 5 Hz. Damping below 30 Hz was successfully achieved. The maximum S/N ratio was calculated 6, improving from 1.8. Simulation showed that the maximum S/N would be 75 under the viscosity damping coefficient of 1 N s/m.