Soft robotic manipulator for intraoperative MRI-guided transoral laser microsurgery.

Magnetic resonance (MR) imaging (MRI) provides compelling features for the guidance of interventional procedures, including high-contrast soft tissue imaging, detailed visualization of physiological changes, and thermometry. Laser-based tumor ablation stands to benefit greatly from MRI guidance because 3D resection margins alongside thermal distributions can be evaluated in real time to protect critical structures while ensuring adequate resection margins. However, few studies have investigated the use of projection-based lasers like those for transoral laser microsurgery, potentially because dexterous laser steering is required at the ablation site, raising substantial challenges in the confined MRI bore and its strong magnetic field. Here, we propose an MR-safe soft robotic system for MRI-guided transoral laser microsurgery. Owing to its miniature size (Ø12 × 100 mm), inherent compliance, and five degrees of freedom, the soft robot ensures zero electromagnetic interference with MRI and enables safe and dexterous operation within the confined oral and pharyngeal cavities. The laser manipulator is rapidly fabricated with hybrid soft and hard structures and is powered by microvolume (<0.004 milliter) fluid flow to enable laser steering with enhanced stiffness and lowered hysteresis. A learning-based controller accommodates the inherent nonlinear robot actuation, which was validated with laser path-following tests. Submillimeter laser steering accuracy was demonstrated with a mean error < 0.20 mm. MRI compatibility testing demonstrated zero observable image artifacts during robot operation. Ex vivo tissue ablation and a cadaveric head-and-neck trial were carried out under MRI, where we employed MR thermometry to monitor the tissue ablation margin and thermal diffusion intraoperatively.

Different types of carbon nanotube-based anodes to improve microbial fuel cell performance.

The microbial fuel cell (MFC) is an innovative technology for producing electricity directly from biodegradable organic matter using bacteria. Among all the influenceable factors, anode materials play a crucial role in electricity generation. Recently, carbon nanotubes (CNTs) have exhibited promising properties as electrode material due to their unique structural, and physical and chemical properties. In this study, the impacts of CNT types in CNT-based anodes were investigated to determine their effect on both efficiency of wastewater treatment and power generation. The CNTs, namely single-walled CNT with carboxyl group (SWCNT), multi-walled CNT with carboxyl group (MWCNT-COOH) and multi-walled CNT with hydroxyl group (MWCNT-OH) were used to fabricate CNT-based anodes by a filtration method. Overall, MWCNTs provided better results than SWCNTs, especially in the presence of the -OH groups. The highest power and treatment efficiencies in MFC were achieved with an anode made of MWCNT-OH filtered on Poreflon membrane; the open circuit voltage attained was 0.75 V and the maximum power density averaged 167 mW/m(2), which was 130% higher than that obtained with plain carbon cloth. In addition, MWCNT-OH is more cost-effective, further suggesting its potential to replace plain carbon cloth generally used for the MFC anode.

Physico-chemical characterisation versus in situ micro-structural characterisation of membrane fouling in membrane bioreactors.

Fouling characteristics of aerobic submerged membrane bioreactors were analysed under two different membrane materials. Polyethersulfone (PES) membranes were found to foul faster at sub-critical flux than polyolefin (PO) membranes. Physico-chemical characterisation, by means of comparison of extracellular polymeric substances (EPS) and soluble microbial products (SMP) concentrations, as well as the mixed liquor suspended solids (MLSS) concentration were unable to explain the differences in membrane fouling of the contrasting membrane materials. The use of confocal laser scanning microscopy (CLSM) to image organic foulants directly on the membrane surface, coupled with image analyses showed that membrane fouling mechanism shifted from a biofilm initiated process on PO membranes to a bio-organic dominated process on PES membranes under sub-critical flux conditions. These results show that physico-chemical characterisation of an MBR process may not effectively distinguish the effectiveness of different membrane materials, so long as operating conditions are identical, and that characterisation of foulants on the membrane surfaces was necessary to elucidate the differences in membrane fouling.

Characterisation of biofilm constituents and their effect on membrane filterability in MBRs.

Fouling is still one of the main issues in the operation of membrane bioreactors (MBRs). While most attention has been paid to extracellular polymeric substances (EPS) and soluble microbial products (SMP) in the bulk solution, changes in membrane filterability may be more adequately described by the structural characteristic of the fouling layer or biofilm. This study shows that membrane filterability and the rise in TMP is associated to the changes in the biofiom structure, and polysaccharides may be the most significant fraction that affects fouling.

Repeated mechanical loading enhances the expression of Indian hedgehog in condylar cartilage.

Indian hedgehog (Ihh) acts as a mechanotransduction mediator that converts mechanical strain into cellular proliferation and cartilage formation in mandibular condylar cartilage. The aim of this study was to examine the effect of repeated mechanical strain on the level of expression of Ihh and type II collagen mRNA in condylar growth. Two hundred and eighty 35 days old Sprague-Dawley rats were divided into 10 experimental and 10 control groups. Repeated mechanical loading was applied by advancing the mandible in a stepwise manner by fitting a stepwise bite jumping appliance. Animals were sacrificed together with their matched controls on 10 different time points. Total RNA was extracted from condylar cartilage immediately after dissection. Ihh and type II collagen mRNA was quantified using real-time PCR. In the experimental group, Ihh mRNA increased significantly on experimental day 7. Upon the second advancement, another peak was elicited 7 days later. Type II collagen showed a significant increase on days 21 and 44 of advancement. This indicated that mechanical loading in a repeated manner, triggers the expression of Ihh which in turn increases the number of replicating mesenchymal cells as well as the amount of the cartilage formed. Taken together these events increase condylar growth.

Brain tissue sodium is a ticking clock telling time after arterial occlusion in rat focal cerebral ischemia.

BACKGROUND AND PURPOSE: Many patients with acute stroke are excluded from receiving thrombolysis agents within the necessary time limit (3 or 6 hours from stroke onset) because they or their family members are unable provide the time of stroke onset. Brain tissue sodium concentration ([Na(+)]) increases gradually and incessantly during the initial hours of experimental focal cerebral ischemia but only in severely damaged brain regions. We propose that this steady increase in [Na(+)] can be used to estimate the time after arterial occlusion in the rat middle cerebral artery occlusion model of ischemic stroke. METHODS: Sixteen anesthetized Sprague-Dawley rats underwent permanent middle cerebral artery occlusion combined with bilateral common artery occlusion. After 100 to 450 minutes, diffusion-weighted MRI was used to generate apparent diffusion coefficient (ADC) maps, cerebral blood flow (CBF) was determined with (14)C-iodoantipyrine (in a subset of 7 animals), and the brain was frozen. Autoradiographic CBF sections and punch samples for Na(+) analysis were obtained from the brain at the same level of the MR image. Severely at risk regions were identified with an ADC of <520 microm(2)/s and, in the subset, with both ADC of <520 microm(2)/s and CBF of <40 mL. 100 g(-1). min(-1). RESULTS: Both CBF and the ADC dropped quickly and remained stable in the initial hours after ischemic onset. Linear regression revealed strong linearity between [Na(+)] and time after onset, with a slope of 0.95 or 1.00 (mEq/kg DW)/min, with both ADC and ADC-plus-CBF criteria, respectively. The 95% CIs at 180 and 360 minutes were between 41 and 52 minutes. CONCLUSIONS: The time after ischemic onset can be estimated with this 2-step process. First, ADC and CBF are used to identify severely endangered regions. Second, the [Na(+)] in these regions is used to estimate time after onset. The favorable 95% CIs at the time limits for thrombolytic therapy and the availability of measurements of ADC, CBF, and [Na(+)] in humans through the use of MRI suggest that this time-estimation scheme could be used to assess the appropriateness of thrombolysis for patients who do not know when the stroke occurred.

Brain activation during human finger extension and flexion movements.

Corticospinal projections to the motor neuron pool of upper-limb extensor muscles have been reported to differ from those of the flexor muscles in humans and other primates. The influence of this difference on the central nervous system control for extension and flexion movements is unknown. Cortical activation during thumb extension and flexion movements of eight human volunteers was measured using functional magnetic resonance imaging (fMRI), which detects signal changes caused by an alteration in the local blood oxygenation level. Although the relative activity of the extensor and flexor muscles of the thumb was similar, the brain volume activated during extension was substantially larger than that during flexion. These fMRI results were confirmed by measurements of EEG-derived movement-related cortical potential. Higher brain activity during thumb extension movement may be a result of differential corticospinal, and possibly other pathway projections to the motoneuron pools of extensor and flexor muscles of upper the extremities.

Postictal in situ MRS brain lactate in the rat kindling model.

OBJECTIVE: To determine the temporal and spatial extent of the lactate (Lact) changes as correlated with seizure characteristics and EEG changes in the rat kindling model. BACKGROUND: Prior studies using MRS have detected cerebral Lact postictally in animal models of seizures and in patients with intractable focal epilepsy. METHODS: We performed MRS in sham control rats (n = 4) and in rats stimulated in the right hippocampus at two different stages of the kindling and at three time points after the seizures: <2 hours (n = 8 and 5, stage 0 and stage 5), 2 to 3 hours (n = 5 and 6), and >3 hours (n = 4 and 2). Lact/creatine (Cr) and N-acetylaspartate (NAA)/Cr ratios were measured in six contiguous voxels (three left, three right) covering the hippocampi, anterior and posterior regions, and compared with EEG and ictal behavior. Lact/Cr ratios were measured at a very low level in the sham control rats and in the >3-hour group. RESULTS: In the <2-hour group, Lact/Cr increase was higher in stage-5 rats as compared with stage-0 rats (p = 0.001, unpaired t-test) and sham control rats when all the voxels were considered. Lact/Cr ratios were higher in the stimulated area as compared with all other brain areas in stage-0 rats (p = 0.05, paired t-test) but not in the stage-5 rats. Similar results with more inter-animal variability were measured in the 2- to 3-hour group. NAA/Cr ratios increased significantly after stage-0 kindling in the stimulated hippocampus but not after stage-5 kindling. CONCLUSIONS: Postictal Lact increase as assayed by MRS correlates with EEG and behavioral seizures and suggests that it would be an additional noninvasive technique for seizure localization during the presurgical evaluation of patients with intractable focal epilepsy.

Vibrio parahemolyticus bacteremia: case report.

Vibrio parahemolyticus (V. parahemolyticus) is a halophilic gram-negative bacillus that lives in the ocean. It is the leading cause of infectious diarrhea in Taiwan and sometimes produces soft tissue infections, but it is rarely a cause of bacteremia. There have been only 11 cases reported in the literature. Most of the cases involved a history of ingestion of seafood or exposure to seawater. In addition, those patients were all immunosuppressed, especially with leukemia and cirrhosis. We report a 60-year-old male patient with chronic hepatitis C and adrenal insufficiency. He developed V. parahemolyticus bacteremia following ingestion of seafood one week prior to admission. His condition was complicated with neck and right lower leg soft tissue infection, as well as multiple organ failure. The patient survived after intravenous ceftazidime, oral doxycycline, and surgical debridement. To our knowledge, this is the 12th reported cases on Medline, and the second bacteremic case in Taiwan. After reviewing the literature, we suggest that all patients with immunosuppressed conditions or adrenal insufficiency should eat foods that are well cooked and avoid raw seafood. Moreover, when patients who are at risk to develop fever, diarrhea, and soft tissue infection after ingestion of seafood, V. parahemolyticus infection should be suspected. All culture specimens should be inoculated on Vibrios selective media.

1H-MRS evidence of neurodegeneration and excess glutamate + glutamine in ALS medulla.

OBJECTIVE: To determine whether short echo-time (TE) proton magnetic resonance spectroscopic imaging (1H-MRSI) can detect in vivo differences in signal intensities of specific metabolites in the medulla of patients with ALS compared with healthy individuals and whether these metabolites could be useful surrogate markers of disease. BACKGROUND: 1H-MRSI can detect N-acetylaspartate + N-acetylaspartylglutamate (abbreviated NAx), which is localized to neurons, and glutamate (Glu) + glutamine (Gln), abbreviated Glx, which may be important in ALS pathogenesis. The medulla is an ideal region to study ALS because of its high density of nuclei and fiber tracts that frequently undergo degeneration, even when more rostral brain regions show minimal pathology. METHODS: Ten patients with ALS and seven healthy control subjects underwent short TE 1H-MRSI on a 1.5 T clinical imaging system. Signal intensities of NAx and Glx were normalized to creatine-phosphocreatine and compared between groups. RESULTS: Compared with normal subjects, the medulla of patients with ALS had 17% lower NAx (p = 0.03) and 55% higher Glx (p = 0.02) signals. Bulbar symptoms, represented by the ALS Functional Rating Scale, correlated with Glx (r = -0.68, p = 0.03) but not NAx (r = 0.22, p = 0.53). CONCLUSION: There is in vivo 1H-MRSI evidence of neuronal degeneration or loss and excess Glu + Gln in the medulla of patients with ALS. Although this cross-sectional study cannot identify which change occurred first, the higher Glx signal in the medulla of patients with more dysarthria and dysphagia is consistent with the hypothesis of Glu excitotoxicity in ALS pathogenesis. Longitudinal 1H-MRSI studies of the medulla (and other brain regions) in more patients with ALS are required to confirm these findings and to determine whether such metabolite changes will be useful in monitoring disease progression, in clinical diagnosis, and in understanding the pathogenesis of ALS.

Beagle 2: a proposed exobiology lander for ESA's 2003 Mars Express mission.

The aim of the proposed Beagle 2 small lander for ESA's 2003 Mars Express mission is to search for organic material on and below the surface of Mars and to study the inorganic chemistry and mineralogy of the landing site. The lander will have a total mass of 60kg including entry, descent, and landing system. Experiments will be deployed on the surface using a robotic arm. It will use a mechanical mole and grinder to obtain samples from below the surface, under rocks, and inside rocks. Sample analysis by a mass spectrometer will include isotopic analysis. An optical microscope, an X-ray spectrometer and a Mossbauer spectrometer will conduct in-situ rock studies.

Neuronal pathology in the wobbler mouse brain revealed by in vivo proton magnetic resonance spectroscopy and immunocytochemistry.

Proton magnetic resonance spectroscopy (1H-MRS) was used to measure the in vivo signal of N-acetylaspartate (NAA), a putative neuronal marker, in the brain of the mutant wobbler mouse, a model of motor neuron disease. The ratio of NAA to creatine-phosphocreatine, an internal standard, was significantly lower in five affected wobbler mice (0.79+/-0.05; mean+/-s.d.) than in five unaffected littermates (0.98+/-0.10, p = 0.006). Ubiquitin and phosphorylated heavy neurofilament immunoreactivities were increased in cortical neurons of affected animals. This is the first demonstration of cerebral neuronal pathology in the wobbler mouse, supporting its use as a model of amyotrophic lateral sclerosis. In vivo IH-MRS and correlative postmortem study of wobbler mouse brain will allow temporal monitoring of neuronal degeneration and responsiveness to neuroprotective pharmacotherapies.

MRS metabolic markers of seizures and seizure-induced neuronal damage.

PURPOSE: Proton magnetic resonance spectroscopy (MRS) was used to identify specific in situ metabolic markers for seizures and seizure-induced neuronal damage. Kainic acid (KA)-induced seizures lead to histopathologic changes in rat brain. The protective effect of cycloheximide treatment against neuronal damage caused by KA-induced seizures was studied, using in situ proton MRS imaging technique. METHODS: Rats were pretreated with placebo or cycloheximide 1 h before KA injection. Rat brains (n = 25) were scanned at the level of the hippocampus before, during, and 24 h after seizures. Spectra were recorded and the relative ratios of N-acetylaspartate (NAA), choline (cho), and lactate (Lac) to creatine (Cr) were calculated and compared between groups. RESULTS: A significant increase in Lac ratios was observed in KA-treated rats during and 24 h after seizure onset and this increase was prevented by cycloheximide pretreatment. NAA ratios were significantly higher during the ictal phase following KA treatment and this effect was not affected by cycloheximide pretreatment. Nissl staining confirmed previously reported prevention of KA-induced neuronal loss in CA3 and CA1 areas of the hippocampus by cycloheximide pretreatment. CONCLUSIONS: Our results suggest that in situ Lac increase is a marker of seizure-induced neuronal damage, whereas N-acetylaspartate (NAA) changes during and after status epilepticus may be a reflection of neuronal activity and damage, respectively.

Oblique proton chemical shift imaging for the presurgical localization of mesial temporal epilepsy.

Precise localization of the epileptogenic zone in patients suffering from mesial temporal lobe epilepsies is a prerequisite for surgery. For this purpose, a scheme for selecting the volume of interest in an oblique plane covering the head, body, and tail of the hippocampal formation (HF) was implemented in a water-suppressed proton chemical shift imaging (CSI) acquisition. This approach, evaluated by consecutively acquired CSI spectra of both temporal lobes, demonstrates that it can potentially be a routine technique for clinical diagnosis. Since the method produces localized spectral detail of the HF, it facilitates a convenient comparison of CSI lateralization to that assessed by HF atrophy (due to sclerosis) using the MRI-volumetry technique.

Cloning and expression of the gene for a protein disulfide oxidoreductase from Azotobacter vinelandii: complementation of an Escherichia coli dsbA mutant strain.

The gene for a disulfide oxidoreductase was cloned and sequenced from Azotobacter vinelandii and termed the dsbA locus. The deduced amino acid sequence contains 214 residues with a potential 17-residue signaling sequence on the N-terminal end. This gives the mature protein a calculated molecular mass of 21 799 Da. The A. vinelandii DsbA protein contains the well-conserved motif of C-P-H-C, which is found in the catalytic site of other bacterial DsbA enzymes. The A. vinelandii dsbA gene was expressed in Escherichia coli and was found to be able to complement an E. coli dsbA mutant strain by restoring flagellar and alkaline phosphatase activities. A. vinelandii dsbA mutant strains were impossible to characterize because of the extreme deleterious effect of the mutation. Therefore, the in vivo role of A. vinelandii DsbA is unknown, but it may function to form disulfide bonds and/or be involved in cytochrome biogenesis.

Temporal changes in proton MRS metabolites after kainic acid-induced seizures in rat brain.

PURPOSE: In situ 1H-magnetic resonance spectroscopy (MRS) was used to study temporal metabolic changes in a rat model of temporal lobe epilepsy (TLE) by using kainic acid (KA). METHODS: Rat brains were scanned at the level of the hippocampal body for MRS measurements. Relative ratios of N-acetyl groups (NA: N-acetylaspartate and N-acetylaspartyl glutamate), choline, and lactate (Lac) over creatine (Cr) were calculated. RESULTS: NA/Cr ratios increased significantly during the ictal phase. During the postictal and interictal phases, the NA/Cr ratio decreased. There was a significant and prolonged increase of the lactate/Cr ratio in the hippocampi of rats that started 1 h after the onset of KA-induced seizure activity and persisted up to 24 h after the injection. The prolonged lactate/Cr increase in an area susceptible to neuronal damage (e.g., hippocampus) correlated with the onset of seizure activity but remained elevated thereafter. CONCLUSIONS: The ictal and early postictal increase in lactate ratios may reflect increased cellular activity and metabolism resulting from KA excitotoxicity. Assuming that the changes in NA/Cr ratios are due to NAA increase, we speculate that an activation of the N-acetylaspartylglutamate (NAAG) dipeptidase pathway may explain the ictal increase in NA/Cr ratios. The late postictal decrease in NA/Cr ratios is a reflection of KA-induced neuronal cell loss.

31P magnetic resonance spectroscopy detection of response-predictive adenosine triphosphate decrease in irradiated radiation-induced fibrosarcoma-1 tumors.

RATIONALE AND OBJECTIVES: In previous phosphorus-31 (31P) magnetic resonance (MR) spectroscopy studies of radiation-induced fibrosarcoma (RIF-1), tumor model single-dose x-ray irradiation was applied at subcurative doses. A more effective x-ray does was used in this study, allowing correlation of treatment efficacy with the early changes observed in the 31P MR spectra of RIF-1 tumors. METHODS: Subcutaneous RIF-1 tumors of 60 mice were examined by 31P MR spectroscopy shortly before a single localized x-ray dose of 40 Gy and at eight times (2, 12, 24, 48, 72, 120, 168, and 216 hours) thereafter. RESULTS: Early increases in the relative concentration of inorganic phosphate and decreases in adenosine triphosphate (ATP), most notably at 2 and 12 hours (each P < 0.00001), were observed that lasted up to 48 hours after irradiation. Phosphomonoester and tumor pH showed decreases that reversed even earlier. Reduction of ATP measured at 48 hours after irradiation was, however, correlated with percent tumor shrinkage observed during the subsequent weeks (r = -0.59; P < 0.00001). CONCLUSIONS: Sustained loss of RIF-1 tumor ATP is predictive of treatment efficacy. Temporary depression of high-energy phosphate in favor of inorganic phosphate does not necessarily lead to cell death.

Postictal alteration of sodium content and apparent diffusion coefficient in epileptic rat brain induced by kainic acid.

PURPOSE: We studied temporal changes of brain sodium and apparent diffusion coefficient (ADC) in a temporal lobe epilepsy (TLE) rat model using kainic acid (KA). METHODS: In situ three-dimensional 23Na magnetic resonance imaging (MRI) and proton diffusion-weighted imaging (DWI) were used. KA at a dose of 10 mg/kg body weight and 12 adult Sprague Dawley rats weighing 228-318 g (268 +/- 25 g) were used. RESULTS: Twenty-four hours after KA injection, magnetic resonance (MR) visible sodium levels increased in both the pyriform cortex (+90%) and amygdala (+68%) and increased insignificantly in the hippocampus (+18%) and caudate-putamen (12%). The ADC in the pyriform cortex showed a -9% decrease at 5 h postictally, reaching -30% at 24 h, whereas in the amygdala decreases were -8 and -26% respectively. A significant decrease in ADC (-7%) in the hippocampus was also observed 24 h postically. Seven days later, sodium increases persisted, whereas ADC returned to normal level. CONCLUSIONS: The increase in MR visible sodium, associated with the decrease in ADC is consistent with the hypothesis that sequential seizures caused an increase in sodium influx and perturbation of membrane ion homeostasis, which eventually evolved into an irreversible phase of cellular edema, with increased MR visible intracellular sodium and decreased ADC. Return of ADC to near-control level and persistent high sodium level at 7 days may be explained by the increase in extracellular space and tissue necrosis.

Oxygenation and metabolic status of KHT tumors as measured simultaneously by 19F magnetic resonance imaging and 31P magnetic resonance spectroscopy.

To evaluate the relationship between the partial pressure of oxygen (pO2) and the energy-related phosphorous metabolites in individual KHT murine sarcomas more clearly, the spatial distributions of pO2 were obtained simultaneously with 31P magnetic resonance spectra, and repeatedly as a function of growth. The pO2 maps, derived from serial images of the spin-lattice relaxation times of sequestered perfluorocarbon emulsions, were heterogeneous spatially, which is characteristic of solid tumors. Collectively, the median pO2 of the seven KHT tumors of mass varying from 0.2 to 1.8 g decreased from 60 to 0 mmHg, but it increased in one of five tumors which were followed in the growth study. The pHMRS and the high-energy ratio of phosphocreatine + nucleoside triphosphates to total observed phosphorous (TP) dropped on average as a function of tumor growth, while the low energy ratio of P(i) to TP increased. Also, for the tumors as a whole, the pH and high-energy ratio increased with increasing median pO2 while the low energy ratio decreased, but the 31P values of some tumors did not follow this general trend. These individual variations suggest the need for simultaneous and repeated measurements of phosphorous metabolites and oxygen tension for complete information regarding the tumor status in experimental studies and therapeutic procedures in humans.