Beamspace dual signal space projection (bDSSP): a method for selective detection of deep sources in MEG measurements.

OBJECTIVE: Magnetoencephalography (MEG) has a well-recognized weakness at detecting deeper brain activities. This paper proposes a novel algorithm for selective detection of deep sources by suppressing interference signals from superficial sources in MEG measurements. APPROACH: The proposed algorithm combines the beamspace preprocessing method with the dual signal space projection (DSSP) interference suppression method. A prerequisite of the proposed algorithm is prior knowledge of the location of the deep sources. The proposed algorithm first derives the basis vectors that span a local region just covering the locations of the deep sources. It then estimates the time-domain signal subspace of the superficial sources by using the projector composed of these basis vectors. Signals from the deep sources are extracted by projecting the row space of the data matrix onto the direction orthogonal to the signal subspace of the superficial sources. MAIN RESULTS: Compared with the previously proposed beamspace signal space separation (SSS) method, the proposed algorithm is capable of suppressing much stronger interference from superficial sources. This capability is demonstrated in our computer simulation as well as experiments using phantom data. SIGNIFICANCE: The proposed bDSSP algorithm can be a powerful tool in studies of physiological functions of midbrain and deep brain structures.

Image Fusion for Radiosurgery, Neurosurgery and Hypofractionated Radiotherapy.

Precise target detection is essential for radiosurgery, neurosurgery and hypofractionated radiotherapy because treatment results and complication rates are related to accuracy of the target definition. In skull base tumors and tumors around the optic pathways, exact anatomical evaluation of cranial nerves are important to avoid adverse effects on these structures close to lesions. Three-dimensional analyses of structures obtained with MR heavy T2-images and image fusion with CT thin-sliced sections are desirable to evaluate fine structures during radiosurgery and microsurgery. In vascular lesions, angiography is most important for evaluations of whole structures from feeder to drainer, shunt, blood flow and risk factors of bleeding. However, exact sites and surrounding structures in the brain are not shown on angiography. True image fusions of angiography, MR images and CT on axial planes are ideal for precise target definition. In malignant tumors, especially recurrent head and neck tumors, biologically active areas of recurrent tumors are main targets of radiosurgery. PET scan is useful for quantitative evaluation of recurrences. However, the examination is not always available at the time of radiosurgery. Image fusion of MR diffusion images with CT is always available during radiosurgery and useful for the detection of recurrent lesions. All images are fused and registered on thin sliced CT sections and exactly demarcated targets are planned for treatment. Follow-up images are also able to register on this CT. Exact target changes, including volume, are possible in this fusion system. The purpose of this review is to describe the usefulness of image fusion for 1) skull base, 2) vascular, 3) recurrent target detection, and 4) follow-up analyses in radiosurgery, neurosurgery and hypofractionated radiotherapy.

Development of a molecularly evolved, highly sensitive CaMKII FRET sensor with improved expression pattern.

Genetically encoded fluorescence resonance energy transfer (FRET) biosensors have been successfully used to visualize protein activity in living cells. The sensitivity and accuracy of FRET measurements directly depend on biosensor folding efficiency, expression pattern, sensitivity, and dynamic range. Here, to improve the folding efficiency of the Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα) FRET biosensor, we amplified the association domain of the CaMKIIα gene using error-prone polymerase chain reaction (PCR) and fused it to the N-terminus of mCherry in a bacterial expression vector. We also created an Escherichia coli expression library based on a previously reported fluorescent protein folding reporter method, and found a bright red fluorescent colony that contained the association domain with four mutations (F394L, I419V, A430T, and I434T). In vitro assays using the purified mutant protein confirmed improved folding kinetics of the downstream fluorescent protein, but not of the association domain itself. Furthermore, we introduced these mutations into the previously reported CaMKIIα FRET sensor and monitored its Ca2+/calmodulin-dependent activation in HeLa cells using 2-photon fluorescence lifetime imaging microscopy (2pFLIM), and found that the expression pattern and signal reproducibility of the mutant sensor were greatly improved without affecting the autophosphorylation function and incorporation into oligomeric CaMKIIα. We believe that our improved CaMKIIα FRET sensor would be useful in various types of cells and tissues, providing data with high accuracy and reproducibility. In addition, the method described here may also be applicable for improving the performance of all currently available FRET sensors.

Optimal hypofractionated conformal radiotherapy for large brain metastases in patients with high risk factors: a single-institutional prospective study.

BACKGROUND: A single-institutional prospective study of optimal hypofractionated conformal radiotherapy for large brain metastases with high risk factors was performed based on the risk prediction of radiation-related complications. METHODS: Eighty-eight patients with large brain metastases ≥10 cm(3) in critical areas treated from January 2010 to February 2014 using the CyberKnife were evaluated. The optimal dose and number of fractions were determined based on the surrounding brain volume circumscribed with a single dose equivalent (SDE) of 14 Gy (V14) to be less than 7 cm(3) for individual lesions. Univariate and multivariate analyses were conducted. RESULTS: As a result of optimal treatment, 92 tumors ranging from 10 to 74.6 cm(3) (median, 16.2 cm(3)) in volume were treated with a median prescribed isodose of 57% and a median fraction number of five. In order to compare the results according to the tumor volume, the tumors were divided into the following three groups: 1) 10-19.9 cm(3), 2) 20-29.9 cm(3) and 3) ≥30 cm(3). The lesions were treated with a median prescribed isodose of 57%, 56% and 55%, respectively, and the median fraction number was five in all three groups. However, all tumors ≥20 cm(3) were treated with ≥ five fractions. The median SDE of the maximum dose in the three groups was 47.2 Gy, 48.5 Gy and 46.5 Gy, respectively. Local tumor control was obtained in 90.2% of the patients, and the median survival was nine months, with a median follow-up period of seven months (range, 3-41 months). There were no significant differences in the survival rates among the three groups. Six tumors exhibited marginal recurrence 7-36 months after treatment. Ten patients developed symptomatic brain edema or recurrence of pre-existing edema, seven of whom required osmo-steroid therapy. No patients developed radiation necrosis requiring surgical resection. CONCLUSION: Our findings demonstrate that the administration of optimal hypofractionated conformal radiotherapy based on the dose-volume prediction of complications (risk line for hypofractionation), as well as Kjellberg's necrosis risk line used in single-session radiosurgery, is effective and safe for large brain metastases or other lesions in critical areas.

Five-fraction CyberKnife radiotherapy for large brain metastases in critical areas: impact on the surrounding brain volumes circumscribed with a single dose equivalent of 14 Gy (V14) to avoid radiation necrosis.

The efficacy and toxicity of five-fraction CyberKnife radiotherapy were evaluated in patients with large brain metastases in critical areas. A total of 85 metastases in 78 patients, including tumors >30 cm(3) (4 cm in diameter) were treated with five-fraction CyberKnife radiotherapy with a median marginal dose of 31 Gy at a median prescribed isodose of 58%. Changes in the neurological manifestations, local tumor control, and adverse effects were investigated after treatment. The surrounding brain volumes circumscribed with 28.8 Gy (single dose equivalent to 14 Gy: V14) were measured to evaluate the risk of radiation necrosis. Neurological manifestations, such as motor weakness, visual disturbances and aphasia improved in 28 of 55 patients (50.9%). Local tumor control was obtained in 79 of 85 metastases (92.9%) during a median follow-up of eight months. Symptomatic edema occurred in 10 patients, and two of them (2.6%) required surgical resection because of radiation necrosis. The V14 of these patients was 3.0-19.7 cm(3). There were 16 lesions with a V14 of ≥7.0 cm(3), and two of these lesions developed extensive brain edema due to radiation necrosis. None of the patients with a V14 of <7.0 cm(3) exhibited edema requiring surgical intervention. We therefore conclude that a high rate of local tumor control and low rates of complications can be obtained after five-fraction CyberKnife radiotherapy for large metastases in critical areas. The V14 of the surrounding brain is therefore a useful indicator for the risk of radiation necrosis in patients with large metastases.

Spinal epidural arteriovenous fistulas with unusual manifestation of sudden onset of severe neurological deficits: case report.

Spinal epidural arteriovenous fistulas with perimedullary venous drainage cause venous hypertension, and usually manifest as slowly progressive myelopathy. We treated two patients presenting with sudden onset of severe neurological deficits. Moreover, in Case 1, the venous drainage was exclusively epidural and no perimedullary venous drainage was present. Angiographic findings of this patient were characterized by a slow-flow fistula with marked retention of the epidural venous drainage. Rapidly progressing thrombosis of the epidural venous plexus may have caused the sudden onset of the symptoms. In Case 2, hematomyelia may also be possibly associated with the sudden onset of the symptoms. Early diagnosis and treatment are essential to achieve favorable outcome in such cases because venous congestion results in irreversible venous infarction within a short period.

Three-fraction CyberKnife radiotherapy for brain metastases in critical areas: referring to the risk evaluating radiation necrosis and the surrounding brain volumes circumscribed with a single dose equivalence of 14 Gy (V14).

The efficacy and toxicity of three-fraction CyberKnife radiotherapy were evaluated in patients with brain metastases in critical areas. One hundred and fifty-nine metastases in 145 patients including tumors >10 cm(3) were treated with three-fraction CyberKnife radiotherapy with a median marginal dose of 27 Gy at a median prescribed isodose of 60%. Changes in the neurological manifestations, local tumor control and adverse effects were investigated after treatment. The surrounding brain volumes circumscribed with 23.1 Gy (single dose equivalence of 14 Gy: V14) were measured to evaluate the risk of adverse effects. Neurological manifestations, such as motor weakness, visual disturbances and aphasia improved in 26 of 97 patients (26.8%). Local tumor control was obtained in 137 of 143 metastases (95.8%) during a median follow-up of 7 months. Nine patients had symptomatic edema and three of them (2.1%) required surgical resection because of radiation necrosis. The V14 of these patients was 4.6-31.5 cm(3). There were 35 lesions with a V14 of 7 cm(3) or more and three of them developed extensive brain edema due to radiation necrosis. None of the patients with a V14 of <7 cm(3) exhibited edema requiring an operation. We therefore conclude that a high rate of local tumor control and low rates of complications are obtained after three-fraction CyberKnife radiotherapy for metastases in critical areas. The V14 of the surrounding brain therefore seems to be a useful indicator for the risk evaluation of radiation necrosis in patients with larger metastases.

Prospective randomized evaluation of gel mat foot pads in the endoscopic suite.

BACKGROUND AND PURPOSE: Several studies that compare open and laparoscopic procedures have demonstrated that the minimally invasive surgeon has greater musculoskeletal pain when compared with open surgeons. The purpose of our study was to demonstrate whether the use of the gel mat in the endoscopic setting offered any ergonomic benefit to the surgeon. MATERIALS AND METHODS: One hundred endoscopic procedures, by 11 different surgeons, were randomized intostudy (use of a gel mat) and control groups. Procedures included both percutaneous nephrolithotomies and ureteroscopies and were randomized without regard to the type or expected length of the procedure. All subjects completed a preoperative, intraoperative, immediate postoperative, and 24-hour postoperative questionnaire. During the procedures, an independent observer recorded the number of intraoperative stretches and positional changes because of discomfort. RESULTS: The mean preoperative metrics for the gel mat and no gel mat groups were similar with the exception of the ≤60-minute group, whose members found the gel mat group starting with greater overall discomfort (1.7 vs 1.3, P=0.0273). In the ≤60 minute group, gel mat use significantly decreased postoperative discomfort (P=0.0435) and improved postoperative energy (P=0.0411). In those procedures >60 minutes, the gel mat improved postoperative discomfort and energy as well as the number of stretches and postural changes during the procedure. CONCLUSION: Application of gel mats in the endoscopic setting improves surgeon overall postoperative discomfort and energy in all cases. For cases >60 minutes duration, gel mats also decrease the number of stretches and postural changes from discomfort. Some of these salutary effects may translate into more efficient surgery and better patient outcomes.

Evaluation of bioimpedance as novel predictor of extracorporeal shockwave lithotripsy success.

BACKGROUND AND PURPOSE: Obesity has been identified as a limitation of extracorporeal shockwave lithotripsy (SWL). The obesity metrics of body mass index (BMI) and skin-to-stone distance (SSD) have been evaluated as predictors of SWL success. While SSD has demonstrated a strong correlation with success, BMI has not. Bioimpedance analysis (BIA) is an accurate way of determining body adiposity. We evaluated fat mass percentage (FMP) as measured by BIA as a predictor of SWL success. PATIENTS AND METHODS: We prospectively collected body composition data using the Imp-DF50 Body Impedance Analyzer on consecutive patients undergoing SWL. All generated variables, including FMP, along with demographics, BMI, stone size, and stone composition, were analyzed. Patients were evaluated for success, defined as no evidence of stones on radiography of the kidneys, ureters, and bladder at follow-up. RESULTS: Fifty-two consecutive patients were enrolled in the study, of which 37 had the necessary metrics to be included in the analysis. Twenty-three (62.2%) patients were stone free while 14 (37.8%) were found to have residual stone at follow-up. There was no difference in sex, stone laterality, mean age, and stone size between the groups. For the success and failure groups, the mean BMI was 25.8 kg/m(2) and 29.8 kg/m(2) (P=0.0091), and mean FMP 24.6% and 32.2% (P=0.0034). On mirrored multivariable analysis, both BMI (OR=0.735, P=0.026) and FMP (OR=0.806, P=0.010) were associated with success. Patients with a FMP ≥35% had a reduced success rate compared with those with a FMP <35% (14% vs 73%, respectively, P=0.0028). CONCLUSIONS: Both BMI and FMP both appear to be independent predictors of success. Based on these findings, a large study examining the relationship between BMI, FMP, SSD, and SWL success is warranted. A preoperative FMP ≥35% is associated with a 14% success rate, and alternative treatment strategies for urolithiasis should be considered.

Can we predict if overactive bladder symptoms will resolve after sling surgery in women with mixed urinary incontinence?

Persistent overactive bladder and urgency urinary incontinence after sling surgery (pubovaginal sling or midurethral sling) in women with mixed urinary incontinence (MUI) is devastating to patients and frustrating to surgeons who perform anti-incontinence surgery. To better predict the outcomes of sling surgery in women with MUI, preoperative parameters need to be examined to accurately predict postsurgical outcomes. In this review article, we will explore recent literature exploring possible preoperative predictors of persistent overactive bladder and urgency urinary incontinence after sling surgery in women with MUI.

Other skull-base tumors.

Therapeutic policy and radiosurgical results for nonvestibular schwannomas and chordomas are reported. Fourteen patients with nonvestibular schwannomas treated with marginal doses of 12-15 Gy were followed for 5-13 years. All patients except one were stable and did not require additional treatments. Seven patients with chordomas were treated with marginal doses of 14-20 Gy. Five of them showed unchanged or decreased size of tumors during the follow-up of 4.5-7 years. Two patients required a second treatment and 1 died due to tumor progression outside of the treatment volume. No adverse effects were experienced in any of these patients. Gamma knife radiosurgery is an effective treatment for nonvestibular schwannomas and chordomas. However, multisession radiosurgery may be required for aggressive chordomas.

Long-term results of Gamma Knife surgery for arteriovenous malformations: 10- to 15-year follow up in patients treated with lower doses.

OBJECT: Several adverse effects such as brain edema, necrosis, arterial stenosis, hemorrhage after obliteration, and delayed cyst formation have been reported as early and late complications of Gamma Knife surgery (GKS) for arteriovenous malformations (AVMs). These adverse effects seem to be decreased in a lower-dose treatment regimen compared with the classic higher margin doses of 25 Gy because the radiation insult to the surrounding tissue is minimized. Long-term results of lower-dose GKS for AVMs are presented. METHODS: One hundred fourteen patients with AVMs were treated with lower-dose GKS (< or = 20-Gy margin dose). There were 68 male and 46 female patients, aged 10 to 68 years (mean 35.4 years). The evaluation of AVM nidi and dose planning were performed using both angiography and MR imaging in all cases to exclude the surrounding brain tissue. The mean margin dose was 19.5 Gy. Total angiographically documented obliteration was achieved in 65 (85.5%) of 76 patients. Eleven patients underwent a second treatment, including staged treatment for large AVMs; total AVM obliteration has been achieved in six of them to date. Of 38 patients in whom no follow-up examination could be performed, 19 of them were healthy and 10 were lost from follow up. Nine patients experienced bleeding during the latency period, and four of them suffered lethal hemorrhage. Symptomatic early complications were extensive brain edema after repeated GKS in one patient and an adverse effect on the internal capsule in one. Delayed cyst formation was found in one patient as a late complication 10 years after treatment. No treatment-related death has been noted to date. CONCLUSIONS: Lower-dose GKS is an effective and safe treatment for patients with AVMs and may decrease long-term adverse effects to the surrounding brain.

Low-dose radiosurgery for large vestibular schwannomas: long-term results of functional preservation.

OBJECT: The author conducted a study to assess the long-term results obtained in patients who underwent GKS for large vestibular schwannomas (> 3 cm in diameter). Facial and cochlear nerve functions were evaluated. METHODS: Twenty consecutive large tumors in 18 patients (including two cases of neurofibromatosus Type 2 [NF2]) were followed for more than 6 years. There were eight tumors that were more than 4 cm in maximum diameter. Microsurgery had already been performed prior to GKS in 11 patients (nine recurrent and two residual tumors). Four patients (including one with NF2) died during the follow-up period of other diseases or by accident. Fourteen of 15 tumors were stable or decreased in size. Microsurgery was performed in one patient 2 years after radiosurgery. Facial nerve function was preserved in all patients and hearing preserved in four of five patients with cochlear nerve function prior to radiosurgery. No adverse effects of radiosurgery have been observed to date. CONCLUSIONS: Gamma knife surgery seems to have a place in the low-dose treatment of selected large vestibular schwannoma in patients with a reasonable chance of retaining facial function and pretreatment hearing level. Patients with severe brainstem compression should first be undergo microsurgery.

Hemorrhage risks and obliteration rates of arteriovenous malformations after gamma knife radiosurgery.

OBJECT: The purpose of this study was to analyze the risk of hemorrhage and the obliteration rate after treatment of patients with arteriovenous malformations (AVMs). METHODS: Between 1991 and 1995, 115 patients were treated using gamma knife radiosurgery (GKS). Surgical planning was based on angiograms and three-dimensional images. The angiographic features of the AVMs and the risk factors for hemorrhage were then evaluated. Hemorrhages occurred in eight patients (7%) 7 to 42 months after GKS. Based on AVM morphology, the rates of hemorrhage were five (7.6%) of 66 for AVMs with a single draining vein, seven (14%) of 66 for AVMs with deep drainage, four (26.7%) of 15 for AVMs with a varix, four (28.6%) of 14 for AVMs with venous obstruction, eight (17.0%) of 47 for high-flow (shunt- and mixed-type) AVMs, and five (35.7%) of 14 for large AVMs with a volume of more than 10 cm3. No hemorrhages were observed in association with low-flow (moyamoya-type) AVMs in this series. Total AVM obliteration was achieved in 81.3% of 80 patients who underwent angiography. The obliteration rate was 91.3% for moyamoyatype AVMs and 67.6% for shunt- and mixed-type AVMs. Early obliteration within 12 months was achieved in 63% of the moyamoya-type AVMs. CONCLUSIONS: Moyamoya-type AVMs seem to be at risk for post-GKS hemorrhage. Intravascular embolization should be considered prior to GKS for mixed- and shunt-type AVMs in an attempt to reduce the hemodynamic stress and thereby decrease the risk of hemorrhage.

Simulating canopy stomatal conductance of winter wheat and its distribution using remote sensing information.

The canopy stomatal movement, a plant physiological process, generally occurs within leaves but its influence on exchange of CO2, water vapor, and sensible heat fluxes between atmosphere and terrestrial ecosystem. Many studies have documented that the interaction between leaf photosynthesis and canopy stomatal conductance is obvious. Thus, information on stomatal conductance is valuable in climate and ecosystem models. In current study, a newly developed model was adopted to calculate canopy stomatal conductance of winter wheat in Huang-Huai-Hai (H-H-H) Plain of China (31.5-42.7 degrees N, 110.0-123.0 degrees E). The remote sensing information from NOAA-AVHRR and meteorological observed data were used to estimate regional scale stomatal conductance distribution. Canopy stomatal conductance distribution pattern of winter wheat on March 18, 1997 was also presented. The developed canopy stomatal conductance model might be used to estimate canopy stomatal conductance in land surface schemes and seems can be acted as a boundary condition in regional climatic model runs.

[An antibody recognizing neuron specific tubulin].

A 20-residue peptide corresponding to the C-terminal amino acid sequence of rat nestin was synthesized by the solid phase method. The anti-peptide antibody (designated Anti-Nes-2) against nestin was prepared. Western blots showed that Anti-Nes-2 recognized not only mouse nestin with a MW of 240 kD but also a band with a MW of 50 kD. N-terminal amino acid sequence showed that this 50 kD protein is alpha-tubulin. Western blots with Anti-Nes-2 and with monoclonal antibodies against alpha- and beta-tubulin revealed that this 50 kD band could only be detected in different stages of mouse brain and in the primary culture of neural precursor cells (NPCs), with higher expression during the development of mouse brain and the maturation of NPCs; whereas alpha- and beta-tubulin were expressed in different cell lines and tissues of adult mouse. Taken together, these results indicate that 50 kD protein recognized by Anti-Nes-2 is a neuron-specific alpha-tubulin and could be a neuron-specific posttranslational modification isotype of alpha-tubulin.

Novel nonsense proteolipid protein gene mutation as a cause of X-linked spastic paraplegia in twin males.

We report a third mutation of the proteolipid protein gene in male Japanese patients with X-linked spastic paraplegia. Although the proteolipid protein gene encodes two myelin proteins, proteolipid protein and DM 20, our W144X mutation resides in the latter part of exon 3 (exon 3B), which is spliced out in DM 20. This mutation may reserve the function of DM 20. Findings in our patients support that this form of spastic paraplesia is allelic to Pelizaeus-Merzbacher disease and that the mild clinical phenotype of this disorder may be related to a mutation within exon 3B of the PLP gene.

Blood coagulation and fibrinolysis in eclamptic patients and their correlation with the clinical signs.

We studied the impact of blood coagulation and fibrinolysis on the clinical features of eclamptic patients (n = 20) in Bangladesh. The variables used were edema, proteinuria, blood pressure, number of convulsions, level of consciousness at the time of admission, thrombin antithrombin complexes (TAT), antithrombin (AT) III (%) activity and antigen, D dimer fibrin degradation product and alpha 2-plasmin inhibitor-plasmin complex (PIC) in plasma. Canonical correlation analysis was made to obtain clinical index, eclampsia index and two coagulation indices. On admission, the mean values of coagulation parameters were AT III activity: 83.2% (range 57-108), TAT complex: 47.6 ng/ml (range 11.5-60), D dimer: 1,693 ng/ml (range 417-8,276) and PIC 1.4 mg/ml (range 0.4-3.3). We found a significant correlation between the eclampsia index and clinical index (r = 0.601; p = 0.01). Gestosis index, clinical index, and eclampsia index have also a strong correlation with the coagulation index (r = 0.695, p < 0.005; r = 0.871, p < 0.0001 and r = 0.805, p < 0.0001, respectively). Coagulation and fibrinolysis were markedly activated in eclampsia. The correlation between the clinical status and coagulation status in this study suggested a close relation between the coagulation and the development and progression of the disease.

[Effect of 6-keto prostaglandin E1 on the ascitic hepatoma-130 in vivo. Comparison with chemotherapeutic agent].

The effect of 6-keto-prostaglandin E1 which has a potential action for antiplatelet aggregation was investigated against AH-130 in vivo in comparison with mitomycin C. The experimental schemes were as follows: Group I: Control, Group II: Thromboxane B2 (0.5 mg/kg, X 8, iv), Group III: 6-keto-PG-E1 (0.5 mg/kg, X 10, iv), Group IV: MMC (1.5 mg/kg, X 1, ip), Group V: 6-keto-PGE1 + MMC (0.5 mg/kg, X 10, iv, + 1.5 mg/kg, X 1, ip). The mean survival days, median survival day, and ILS% for 60 days disclosed an inhibitory effect of 6-keto-PGE1, 6-keto-PGE1 + MMC on AH-130 tumor cell growth. By contrast, TXB2, had a promoting effect on AH-130 tumor cell growth. It is concluded that 6-keto-PGE1 which has a structure activity relationship with antitumor agents, such as MMC, Diketocoriolin B, etc., played an important inhibitory role in tumor cell growth in AH-130 in vivo, particularly in combination with the antitumor agents, MMC.