Incidence and Risk Factors of Iatrogenic Retinal Breaks: 20-Gauge versus 25-Gauge Vitrectomy for Idiopathic Macular Hole Repair.

PURPOSE: We compared the incidences of iatrogenic retinal breaks and postoperative retinal detachment between eyes that underwent 20-gauge vitrectomy and those that underwent 25-gauge vitrectomy for idiopathic macular hole repair. METHODS: This retrospective nonrandomized consecutive observational case series included 185 eyes of 183 patients (130 eyes of 129 patients and 55 eyes of 54 patients in the 20- and 25-gauge groups, respectively). We assessed the relationship between the incidence of retinal breaks and postoperative retinal detachment and related this to posterior vitreous detachment and lattice degeneration. RESULTS: The incidences of iatrogenic retinal breaks were 36.9% and 12.7% in the 20-gauge and 25-gauge groups, respectively. These groups did not differ in their respective frequencies of posterior vitreous detachment (the 20-gauge group: 31.5% and the 25-gauge group: 27.3%) and lattice degeneration (the 20-gauge group: 14.6% and the 25-gauge group: 7.3%). Among eyes without lattice degeneration, the 20-gauge group showed a higher incidence of iatrogenic retinal breaks than the 25-gauge group. However, among the eyes with lattice degeneration, the frequency of retinal breaks did not differ between the two surgery types, and four cases of postoperative retinal detachment were reported in both groups. CONCLUSIONS: The incidence of retinal breaks related to idiopathic macular hole surgery is higher among patients undergoing 20-gauge vitrectomy than among those undergoing 25-gauge vitrectomy. Posterior vitreous detachment and lattice degeneration are associated with considerably increased incidences of retinal break.

A free radical scavenger edaravone suppresses systemic inflammatory responses in a rat transient focal ischemia model.

A free radical scavenger edaravone is clinically used in Japan for acute stroke, and several basic researches have carefully examined the mechanisms of edaravone's protective effects. However, its actions on pro-inflammatory responses under stroke are still understudied. In this study, we subjected adult male Sprague-Dawley rats to 90-min middle cerebral artery (MCA) occlusion followed by reperfusion. Edaravone was treated twice via tail vein; after MCA occlusion and after reperfusion. As expected, edaravone-treated group showed less infarct volume and edema formation compared with control group at 24-h after an ischemic onset. Furthermore, edaravone reduced the levels of plasma interleukin (IL)-1ß and matrix metalloproteinase-9 at 3-h after ischemic onset. Several molecules besides IL-1ß and MMP-9 are involved in inflammatory responses under stroke conditions. Therefore, we also examined whether edaravone treatment could decrease a wide range of pro-inflammatory cytokines/chemokines by testing rat plasma samples with a rat cytokine array. MCAO rats showed elevations in plasma levels of CINC-1, Fractalkine, IL-1α, IL-1ra, IL-6, IL-10, IP-10, MIG, MIP-1α, and MIP-3α, and all these increases were reduced by edaravone treatment. These data suggest that free radical scavengers may reduce systemic inflammatory responses under acute stroke conditions, and therefore, oxidative stress can be still a viable target for acute stroke therapy.

Synthesis and biological evaluation of novel orally available 1-phenyl-6-aminouracils containing dimethyldihydrobenzofuranol structure for the treatment of allergic skin diseases.

We have designed and efficiently synthesized novel 1-phenyl-6-aminouracils by replacing the chroman moiety in CX-659S, a nonsteroidal dermatologic candidate, with dimethyldihydrobenzofuranol to cancel CX-659S asymmetric center. Medicinal chemistry effort culminated in the discovery of 13d bearing a 3-methyl group at the 1-phenyl group as a promising compound. Compound 13d, having good in vitro ADME profile and moderate oral bioavailability in mice, showed potent anti-inflammatory activity against hapten-induced contact hypersensitivity reaction in mice following topical and oral administration. The effects of 13d were equipotent to that of tacrolimus or prednisolone. In addition, compound 13d, having potent hydroxyl radical-scavenging activity, showed more potent suppressive effect on substance P-induced pruritus in mice than oxatomide.

Effects of enriched environment on hippocampal neuronal cell death and neurogenesis in rat global ischemia.

Enriched environments reportedly show neuroprotective effects. Here, we evaluated the effect of an enriched environment prior to cerebral ischemia on neuronal cell death and neurogenesis in rats. Male SD rats were housed under standard conditions (SC) or in an enriched environment (EE), then subjected to global ischemia. The Y-maze test and novel object cognition test were used to evaluate cognitive function before and after ischemia. At 7 days post-ischemia, we evaluated hippocampal neuronal cell death with Fluoro-Jade B staining and neurogenesis with BrdU staining. Phosphorylated cAMP response element-binding protein (phospho-CREB) was also evaluated immunohistochemically. The EE + ischemia group showed a significant decrease of cell death post-ischemia compared with the SC + ischemia group. There was no difference in neurogenesis post-ischemia between SC + ischemia and EE + ischemia. The EE + ischemia group showed a significant increase of performance before and after ischemia compared with the SC + ischemia group. Phospho-CREB-positive cells were significantly increased post-ischemia in EE + ischemia compared with SC + ischemia. EE suppressed hippocampal cell death due to global ischemia. Additionally, enhancement of cognitive function before and after ischemia and prevention of cognitive impairment associated with ischemia were observed compared with the controls (rats housed in SC without ischemia). The CREB pathway may play an important role in protection of cognitive ability.

Monitoring of hemodynamic change in patients with carotid artery stenosis during the tilt test using wearable near-infrared spectroscopy.

Transient ischemic attack (TIA) is a major complication in patients with carotid artery stenosis. Patients with severe stenosis sometimes complain of orthostatic dizziness, such as syncope. The purpose of this study was to examine the usefulness of near-infrared spectroscopy (NIRS) for evaluating cerebral circulation in patients with carotid artery stenosis during head-up tilt test (HUTT). Fourteen patients with carotid artery stenosis and nine normal control subjects participated. In addition to blood pressure monitoring, hemoglobin (Hb) values (oxy-Hb, deoxy-Hb, and total Hb) were recorded by a wearable NIRS instrument with a high time resolution during HUTT. Oxy-Hb, which decreased initially when the test table was elevated, subsequently increased in normal volunteers and patients with carotid artery stenosis and did not differ significantly between the two groups. However, the oxy-Hb reduction in the carotid artery stenosis group (-0.02 ± 0.03 a.u.) at 30 s after elevation of the table was significantly larger than in the normal group (0.02 ± 0.02 a.u., P < 0.01). Our results indicate that oxy-Hb reduction in patients with carotid artery stenosis may be related to orthostatic dizziness. We concluded that NIRS monitoring is useful for evaluating cerebral autoregulation in patients with severe carotid artery stenosis.

Delayed inhibition of c-Jun N-terminal kinase worsens outcomes after focal cerebral ischemia.

The stress-activated protein kinase c-Jun N-terminal kinase (JNK) is a central regulator in neuronal death cascades. In animal models of cerebral ischemia, acute inhibition of JNK reduces infarction and improves outcomes. Recently however, emerging data suggest that many neuronal death mediators may have biphasic properties-deleterious in the acute stage but potentially beneficial in the delayed stage. Here, we hypothesized that JNK may also have biphasic actions, so some caution may be required in the development of JNK inhibitors for stroke. Sprague Dawley rats underwent 90 min transient occlusions of the middle cerebral artery. Acute treatment (10 min poststroke) with the JNK inhibitor SP600125 reduced infarction volumes. In contrast, delayed treatment (7 d poststroke) worsened infarction volumes and neurological outcomes. Immunostaining of peri-infarct cortex showed that JNK inhibition suppressed surrogate markers of neurovascular remodeling, including matrix metalloproteinase-9 in GFAP-positive astrocytes and microvascular density. Consistent with these in vivo data, SP600125 significantly suppressed in vitro angiogenesis in rat brain endothelial cultures. Our data provide initial proof-of-concept that the neuronal death target JNK may also participate in endogenous processes of neurovascular remodeling and recovery after cerebral ischemia.

[Progress in NIRS monitoring of cerebral blood flow].

Various studies have demonstrated the usefulness of near infrared spectroscopy (NIRS) for detecting cerebral ischemia during a carotid endarterectomy; however, it is difficult to apply NIRS to the diagnosis of ischemic stroke, since commercially available NIRS, which uses continuous-wave light, does not provide quantitative values of baseline hemoglobin (Hb) concentrations. In contrast, time-resolved near-infrared spectroscopy (TRS) permits quantitative measurement of Hb concentrations. We applied TRS to detection of cerebra vasospasm after subarachnoid hemorrhage (SAH). We investigated 11 age-matched controls and 14 aneurysmal SAH patients that comprised 10 patients with World Federation of Neurological Societies (WFNS) grade V and 4 patients with WFNS grade II. Employing TR-NIRS, we measured the cortical oxygen saturation (CoSO2) and baseline Hb concentrations in the middle cerebral artery territory. The CoSO2 and Hb concentrations remained stable after SAH in 6 patients; digital subtraction angiography (DSA) did not reveal vasospasm in these patients. In 8 patients, however, CoSO2 and total Hb decreased abruptly between 5 and 9 days after SAH. DSA revealed diffuse vasospasms in 6 of 8 patients. The reduction of CoSO2 predicted occurrence of vasospasm at a cutoff value of 3.9%-6.4% with 100% sensitivity and 85.7% specificity. Trans cranial Doppler (TCD) failed to detect vasospasm in 4 cases, whereas TR-NIRS could. Finally, TRS performed on day 1 after SAH revealed significantly higher CoSO2 than that of the controls (p = 0.048), but there was no significant difference in total Hb. TRS detected vasospasm by evaluating the CBO in the cortex and may be more sensitive than TCD, which assesses the blood flow velocity in the M1 portion. TRS may be useful for the diagnosis of ischemic events in stroke patients.

Effect of normobaric oxygen therapy in a rat model of intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Normobaric oxygen (NBO) therapy may be neuroprotective in acute ischemic stroke. However, how NBO may affect intracerebral hemorrhage is unclear. We tested NBO in a rat model of striatal intracerebral hemorrhage. METHODS: Intracerebral hemorrhage was induced by stereotactic injection of collagenase Type VII (0.5 U) into the right striatum of male Sprague-Dawley rats. One hour later, rats were randomized into controls (n=13) versus NBO treatment (n=13). NBO was applied for 2 hours. Hemorrhagic blood volume, brain water content, and neurological outcomes (forelimb placement test, forelimb asymmetry, neuroscore) were quantified at 72 hours. Experiments were repeated in a second independent laboratory to assess reproducibility in neurological outcomes (n=10 per group). RESULTS: NBO did not worsen hemorrhage severity or brain edema. There were no significant differences in hemorrhagic blood volumes (control, 6.4±0.9 µL versus NBO, 7.0±2.1 µL; P=0.18) or brain water content (control, 81.9%±1.1% versus NBO, 81.6%±0.5%; P=0.58). NBO did not affect any of the neurological outcome tests in the primary or secondary studies. CONCLUSIONS: NBO therapy may not worsen outcomes in intracerebral hemorrhage.

Intraoperative EC-IC bypass blood flow assessment with indocyanine green angiography in moyamoya and non-moyamoya ischemic stroke.

OBJECTIVE: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis has been used in moyamoya disease (MD) and non-moyamoya ischemic stroke (non-MD). It is important to monitor hemodynamic changes caused by bypass surgery for postoperative management. We evaluated the bypass blood flow during STA-MCA anastomosis by using indocyanine green (ICG) fluorescence angiography. METHODS: We evaluated the bypass blood flow in 13 MD and 21 non-MD patients during STA-MCA anastomosis by means of ICG angiography with injection of ICG into the anastomosed STA. The ICG perfusion area was calculated when the ICG fluorescence intensity reached maximum. We measured cortical oxygen saturation before anastomosis by means of visual light spectroscopy. RESULTS: ICG angiography demonstrated bypass blood flow from the anastomosed STA to the cortical vessels in all patients. The ICG perfusion area in MD (20.7 ± 6.6 cm(2)) was significantly larger than that in non-MD (8.4 ± 9.1 cm(2), P < 0.05). The cortical oxygen saturation (58.9% ± 8.3%) in MD was significantly lower than that in non-MD (73.4% ± 9.5%, P < 0.05). CONCLUSIONS: ICG angiography with injection of ICG into the bypass artery allowed quantitative assessment of bypass blood flow. The bypass supplies blood flow to a greater extent in MD than in non-MD during surgery. This might be caused by a larger pressure gradient between the anastomosed STA and recipient vessels in MD. These observations indicate that MD requires careful control of systemic blood pressure after surgery to avoid cerebral hyperperfusion syndrome. ICG angiography is considered useful for facilitating safe and accurate bypass surgery and providing information for postoperative management.

Effect of transient forebrain ischemia on flavoprotein autofluorescence and the somatosensory evoked potential in the rat.

In order to evaluate the effect of cerebral ischemia on the flavoprotein fluorescence (FPF), we compared the changes in the FPF and somatosensory evoked potential (SEP) during transient cerebral ischemia in the rat. We measured the FPF and SEP simultaneously via a cranial window made over the right sensorimotor cortex during the left median nerve stimulation in F344 rats. We compared change in FPF and SEP during cerebral ischemia for 60 min. The rCBF were rapidly recovered after reperfusion. However, the recovery rates of the FPF were significantly faster than those of the SEP after reperfusion. These findings indicate that activity-dependent changes of the FPF do not necessarily correlate with the electrical activity after transient cerebral ischemia.

Changes of evoked cerebral blood oxygenation and optical pathlength in the frontal lobe during language tasks: a study by multi-channel, time-resolved near-infrared spectroscopy and functional MRI.

To determine the alterations in optical characteristics and cerebral blood oxygenation (CBO) in the frontal lobe during language tasks, we evaluated the changes in mean optical pathlength (MOP) and CBO induced by a verbal fluency task (VFT) in the right and left frontal lobes in normal adults (n = 9, mean age = 29.6 +/- 4.8 years). We employed a newly developed 8-channel time-resolved near-infrared spectroscopy (TRS) instrument. The results demonstrated differences in MOP in the fronto-temporal areas with subject and wavelength; however, there was no significant difference between the right and left sides (p > 0.05). Also, the VFT did not affect the MOP significantly as compared to that before the tasks (p > 0.05). In all of the recording regions, the VFT caused increases in concentration of oxyhemoglobin and total hemoglobin associated with a decrease in deoxyhemoglobin concentration, indicating that these cortical areas were activated by the VFT. However, the mean concentration changes of oxyhemoglobin and total hemoglobin on the left side were larger than those on the right side. In addition, functional MRI demonstrated that the inferior frontal gyrus on the left side was activated in the subjects who exhibited increases in oxyhemoglobin concentration in these areas. These results suggest that TRS may be useful to study language function and to assess hemispheric dominance for language.

EC-IC bypass function in Moyamoya disease and non-Moyamoya ischemic stroke evaluated by intraoperative indocyanine green fluorescence angiography.

Indocyanine green (ICG) emits near-infrared fluorescence when it is excited by near-infrared light. The near infrared fluorescence of ICG was applied to the imaging of cerebral vessels during neurosurgical operations such as clipping of aneurysms. In this study, ICG angiography was applied to extracranial-intracranial (EC-IC) bypass surgery to evaluate the hemodynamic changes induced by bypass in moyamoya disease (MD) and non-moyamoya ischemic diseases (non-MD). These patients underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. We compared the cortical areas where the bypass supplied blood flow between MD and non-MD. ICG angiography clearly demonstrated the bypass blood flow from the anastomosed STA to the cortical vessels including arteries, capillaries, and veins in both MD and non-MD. Interestingly, the anastomosed STA supplied blood flow to a larger cortical area in MD than non-MD. The bypass supplied greater extent of blood flow to the ischemic brain in MD than in non-MD. This difference might be caused by the fact that the perfusion pressure was lower in MD than in non-MD.

Effects of revascularisation on evoked cerebral blood oxygenation responses in stroke patients.

We demonstrated that ischemic strokes exhibit an increase of deoxyhemoglobin during activation. We evaluated the effect of revascu-larization on the abnormal evoked cerebral blood oxygenation (CBO) re-sponses in these patients, employing near-infrared spectroscopy (NIRS). We selected five patients who exhibited an increase of deoxyhemoglobin associated with increases of oxyhemoglobin and total hemoglobin during activation for this study. These patients showed marked reductions of base-line regional cerebral blood flow and cerebrovascular reserve capacity, which were improved 1 week after revascularization. Postoperative NIRS demonstrated that the increase of deoxyhemoglobin during activa-tion was not observed after revascularization. This preliminary study demonstrated that the abnormal evoked-CBO response in ischemic stroke patients could be improved by revascularization.

Combination therapy with normobaric oxygen (NBO) plus thrombolysis in experimental ischemic stroke.

BACKGROUND: The widespread use of tissue plasminogen activator (tPA), the only FDA-approved acute stroke treatment, remains limited by its narrow therapeutic time window and related risks of brain hemorrhage. Normobaric oxygen therapy (NBO) may be a useful physiological strategy that slows down the process of cerebral infarction, thus potentially allowing for delayed or more effective thrombolysis. In this study we investigated the effects of NBO started simultaneously with intravenous tPA, in spontaneously hypertensive rats subjected to embolic middle cerebral artery (MCA) stroke. After homologous clot injection, animals were randomized into different treatment groups: saline injected at 1 hour; tPA at 1 hour; saline at 1 hour plus NBO; tPA at 1 hour plus NBO. NBO was maintained for 3 hours. Infarct volume, brain swelling and hemorrhagic transformation were quantified at 24 hours. Outcome assessments were blinded to therapy. RESULTS: Upon clot injection, cerebral perfusion in the MCA territory dropped below 20% of pre-ischemic baselines. Both tPA-treated groups showed effective thrombolysis (perfusion restored to nearly 100%) and smaller infarct volumes (379 +/- 57 mm3 saline controls; 309 +/- 58 mm3 NBO; 201 +/- 78 mm3 tPA; 138 +/- 30 mm3 tPA plus NBO), showing that tPA-induced reperfusion salvages ischemic tissue and that NBO does not significantly alter this neuroprotective effect. NBO had no significant effect on hemorrhagic conversion, brain swelling, or mortality. CONCLUSION: NBO can be safely co-administered with tPA. The efficacy of tPA thrombolysis is not affected and there is no induction of brain hemorrhage or edema. These experimental results require clinical confirmation.

Optical topography can predict occurrence of watershed infarction during carotid endarterectomy: technical case report.

BACKGROUND: The major risk of CEA is perioperative stroke. NIRS can detect ischemic changes during CEA; however, possible watershed-type perfusion defects may not be detected by single-channel NIRS occurring at some distance from the light source. In the present case, we tested the usefulness of optical topography (ie, multichannel NIRS, OT) for this purpose. CASE DESCRIPTION: The patient (64-year-old man) exhibited nonsymptomatic 80% stenosis of the right ICA with normal cerebral perfusion. CEA was performed to prevent cerebral infarction. We used single-channel NIRS and OT for monitoring of perfusion changes during CEA. The optodes of OT were placed on the skull to cover the frontal and parietal lobes on the right side, whereas the sensor of the single-channel NIRS was placed on the right forehead. The single-channel NIRS detected no significant perfusion changes during surgery. However, the OT revealed occurrence of watershed-type perfusion defects in the border region between the right middle and posterior cerebral artery supply areas during cross-clamping of the right internal carotid artery. Postoperative MRI showed an ischemic region which corresponded to the area associated with the perfusion defects. CONCLUSION: OT could detect watershed-type posterior perfusion defects which the single-channel NIRS failed to detect. OT may represent a useful tool for intraoperative monitoring during CEA.

Novel piperidinylpyrimidine derivatives as inhibitors of HIV-1 LTR activation.

Piperidinylpyrimidine derivatives, previously prepared as inhibitors of TNF-alpha production, were evaluated for their inhibitory activity against HIV-1 LTR activation. Some of these derivatives inhibited activation of HIV-1 LTR-directed CAT gene expression induced by PMA in Jurkat cells. In this report, we describe SAR in this series of compounds and show that the 3,4-methylenedioxybenzoyl (piperonyloyl) group on the nitrogen of piperidine and lipophilic substitution at the C(6)-position of pyrimidine are important for this inhibitory activity. Some of the synthesized compounds also inhibited HIV-1 LTR transactivation induced by viral protein Tat. These results suggest that piperidinylpyrimidines are useful as potent AIDS therapeutics that directly inhibit HIV-1 LTR activation and indirectly suppress TNF-alpha production.

Comparison of blood-oxygen-level-dependent functional magnetic resonance imaging and near-infrared spectroscopy recording during functional brain activation in patients with stroke and brain tumors.

Blood-oxygen-level-dependent contrast functional magnetic resonance imaging (BOLD-fMRI) has been used to perform functional imaging in brain disorders such as stroke and brain tumors. However, recent studies have revealed that BOLD-fMRI does not image activation areas correctly in such patients. To clarify the characteristics of the evoked cerebral blood oxygenation (CBO) changes occurring in stroke and brain tumors, we have been comparing near-infrared spectroscopy (NIRS) and BOLD-fMRI recording during functional brain activation in these patients. We review our recent studies and related functional imaging studies on the brain disorders. In the primary sensorimotor cortex (PSMC) on the nonlesion side, the motor task consistently caused a decrease of deoxyhemoglobin (deoxy-Hb) with increases of oxyhemoglobin (oxy-Hb) and total hemoglobin (t-Hb), which is consistent with the evoked CBO response observed in normal adults. BOLD-fMRI demonstrated robust activation areas on the nonlesion side. In stroke patients, severe cerebral ischemia (i.e., misery perfusion) caused an increase of deoxy-Hb during the task, associated with increases of oxy-Hb and t-Hb, in the PSMC on the lesion side. In addition, the activation volume of BOLD-fMRI was significantly reduced on the lesion side. The BOLD signal did not change in some areas of the PSMC on the lesion side, but it tended to decrease in other areas during the tasks. In brain tumors, BOLD-fMRI clearly demonstrated activation areas in the PSMC on the lesion side in patients who displayed a normal evoked CBO response. However, the activation volume on the lesion side was significantly reduced in patients who exhibited an increase of deoxy-Hb during the task. In both stroke and brain tumors, false-negative activations (i.e., marked reductions of activation volumes) in BOLD imaging were associated with increases of deoxy-Hb, which could cause a reduction in BOLD signal. BOLD-fMRI investigations of patients with brain disorders should be performed while giving consideration to atypical evoked CBO changes.

Effects of cerebral ischemia on evoked cerebral blood oxygenation responses and BOLD contrast functional MRI in stroke patients.

BACKGROUND AND PURPOSE: To evaluate the mechanisms of failure of blood oxygenation level-dependent (BOLD) imaging in stroke, we compared the evoked cerebral blood oxygenation (CBO) responses and activation volumes (AVs) of BOLD functional MRI (fMRI) in chronic stroke patients with moderate and severe cerebral ischemia. METHODS: We measured the evoked CBO responses in the primary sensorimotor cortex (PSMC) by means of near-infrared spectroscopy during contralateral motor tasks. We compared the AV of BOLD-functional MRI in the PSMC on the nonlesion and lesion sides. Single-photon emission computed tomography was used to classify ischemic status as moderate (slight reduction of regional cerebral blood flow and cerebrovascular reserve capacity [CVRC]) or severe (marked reduction of regional cerebral blood flow and CVRC; ie, misery perfusion). RESULTS: In age-matched controls, deoxyhemoglobin concentration decreased with concomitant increases in oxyhemoglobin and total hemoglobin concentrations during activation. The PSMC on the nonlesion side exhibited a normal CBO response pattern. On the lesion side, moderate cerebral ischemia did not affect the CBO response pattern, but severe cerebral ischemia caused an increase of deoxyhemoglobin during the task, associated with increases of oxyhemoglobin and total hemoglobin. Moderate cerebral ischemia induced only a slight reduction of the AV on the lesion side; however, severe cerebral ischemia markedly reduced the AV on the lesion side. The BOLD signal did not change in some areas of the PSMC on the lesion side in severe cerebral ischemia, whereas it tended to decrease in other areas during the tasks. CONCLUSIONS: Misery perfusion caused a marked reduction of the AV on BOLD imaging, associated with an increase of deoxyhemoglobin concentration during activation. BOLD-fMRI investigations of stroke patients should be performed while giving consideration to baseline circulatory status. Functional near-infrared spectroscopy could be an alternative means to assess the CVRC.

Changes of cerebral blood oxygenation and optical pathlength during activation and deactivation in the prefrontal cortex measured by time-resolved near infrared spectroscopy.

To determine the alterations in optical characteristics and cerebral blood oxygenation (CBO) during activation and deactivation, we evaluated the changes in mean optical pathlength (MOP) and CBO induced by a verbal fluency task (VFT) and driving simulation in the right and left prefrontal cortex (PFC), employing a newly developed time-resolved near infrared spectroscopy, which allows quantitative measurements of the evoked-CBO changes by determining the MOP with a sampling time of 1 s. The results demonstrated differences in MOP in the foreheads with the subjects and wavelength; however, there was no significant difference between the right and left foreheads (p > 0.05). Also, both the VFT and driving simulation task did not affect the MOP significantly as compared to that before the tasks (p > 0.05). In the bilateral PFCs, the VFT caused increases of oxyhemoglobin and total hemoglobin associated with a decrease of deoxyhemoglobin, while the driving simulation task caused decreases of oxyhemoglobin and total hemoglobin associated with an increase of deoxyhemoglobin; there were no significant differences in evoked-CBO changes between the right and left PFC. The present results will be useful for quantitative measurement of hemodynamic changes during activation and deactivation in the adults by near infrared spectroscopy.

Application of multichannel near-infrared spectroscopic topography to physiological monitoring of the cortex during cortical mapping: technical case report.

BACKGROUND: Cortical stimulation via a subdural grid electrode (SGE) is one of the most reliable methods for identifying eloquent areas before surgery. However, the physiological conditions of the cortex during stimulation cannot be monitored electrophysiologically because of electrical artifacts. In the present case, we tested whether or not multichannel near-infrared spectroscopy (NIRS) topography, a noninvasive optical imaging technique, is applicable for monitoring the physiological conditions of the stimulated cortex. CASE DESCRIPTION: The patient (a 27-year-old right-handed man) suffered from glioma in the left frontal lobe. For preoperative cortical mapping, SGEs were implanted over the left motor cortex before tumor resection. Employing NIRS topography, we undertook 2 dimensional imaging of the changes in oxyhemoglobin (Oxy-Hb) and deoxyhemoglobin (Deoxy-Hb) concentration during electrical stimulation. Five-hertz stimulation with 5 mA at the left-hand area produced a localized increase in Oxy-Hb and a decrease in Deoxy-Hb, associated with slight twitching of the right hand. In contrast, 50-Hz stimulation produced significant increases in both Oxy-Hb and Deoxy-Hb at the stimulation site, and the area with such cerebral blood oxygenation (CBO) changes propagated beyond the hand area associated with prominent muscle contractions of the right upper extremity, suggesting that 50-Hz stimulation caused epileptic discharge. CONCLUSION: Near-infrared spectroscopy topography may represent a useful tool for imaging the degree and extent of the physiological effects of electrical stimulation on the cortex, and permits safe and accurate cortical mapping.