Auditory prediction and prediction error responses evoked through a novel cascade roving paradigm: a human ECoG study.

Auditory sensory processing is assumed to occur in a hierarchical structure including the primary auditory cortex (A1), superior temporal gyrus, and frontal areas. These areas are postulated to generate predictions for incoming stimuli, creating an internal model of the surrounding environment. Previous studies on mismatch negativity have indicated the involvement of the superior temporal gyrus in this processing, whereas reports have been mixed regarding the contribution of the frontal cortex. We designed a novel auditory paradigm, the "cascade roving" paradigm, which incorporated complex structures (cascade sequences) into a roving paradigm. We analyzed electrocorticography data from six patients with refractory epilepsy who passively listened to this novel auditory paradigm and detected responses to deviants mainly in the superior temporal gyrus and inferior frontal gyrus. Notably, the inferior frontal gyrus exhibited broader distribution and sustained duration of deviant-elicited responses, seemingly differing in spatio-temporal characteristics from the prediction error responses observed in the superior temporal gyrus, compared with conventional oddball paradigms performed on the same participants. Moreover, we observed that the deviant responses were enhanced through stimulus repetition in the high-gamma range mainly in the superior temporal gyrus. These features of the novel paradigm may aid in our understanding of auditory predictive coding.

Auditory prediction errors in sound frequency and duration generated different cortical activation patterns in the human brain: an ECoG study.

Sound frequency and duration are essential auditory components. The brain perceives deviations from the preceding sound context as prediction errors, allowing efficient reactions to the environment. Additionally, prediction error response to duration change is reduced in the initial stages of psychotic disorders. To compare the spatiotemporal profiles of responses to prediction errors, we conducted a human electrocorticography study with special attention to high gamma power in 13 participants who completed both frequency and duration oddball tasks. Remarkable activation in the bilateral superior temporal gyri in both the frequency and duration oddball tasks were observed, suggesting their association with prediction errors. However, the response to deviant stimuli in duration oddball task exhibited a second peak, which resulted in a bimodal response. Furthermore, deviant stimuli in frequency oddball task elicited a significant response in the inferior frontal gyrus that was not observed in duration oddball task. These spatiotemporal differences within the Parasylvian cortical network could account for our efficient reactions to changes in sound properties. The findings of this study may contribute to unveiling auditory processing and elucidating the pathophysiology of psychiatric disorders.

Region-specific DNA hydroxymethylation along the malignant progression of IDH-mutant gliomas.

The majority of low-grade isocitrate dehydrogenase-mutant (IDHmt) gliomas undergo malignant progression (MP), but their underlying mechanism remains unclear. IDHmt gliomas exhibit global DNA methylation, and our previous report suggested that MP could be partly attributed to passive demethylation caused by accelerated cell cycles. However, during MP, there is also active demethylation mediated by ten-eleven translocation, such as DNA hydroxymethylation. Hydroxymethylation is reported to potentially contribute to gene expression regulation, but its role in MP remains under investigation. Therefore, we conducted a comprehensive analysis of hydroxymethylation during MP of IDHmt astrocytoma. Five primary/malignantly progressed IDHmt astrocytoma pairs were analyzed with oxidative bisulfite and the Infinium EPIC methylation array, detecting 5-hydroxymethyl cytosine at over 850,000 locations for region-specific hydroxymethylation assessment. Notably, we observed significant sharing of hydroxymethylated genomic regions during MP across the samples. Hydroxymethylated CpGs were enriched in open sea and intergenic regions (p < 0.001), and genes undergoing hydroxymethylation were significantly associated with cancer-related signaling pathways. RNA sequencing data integration identified 91 genes with significant positive/negative hydroxymethylation-expression correlations. Functional analysis suggested that positively correlated genes are involved in cell-cycle promotion, while negatively correlated ones are associated with antineoplastic functions. Analyses of The Cancer Genome Atlas clinical data on glioma were in line with these findings. Motif-enrichment analysis suggested the potential involvement of the transcription factor KLF4 in hydroxymethylation-based gene regulation. Our findings shed light on the significance of region-specific DNA hydroxymethylation in glioma MP and suggest its potential role in cancer-related gene expression and IDHmt glioma malignancy.

Ki-67 labeling index predicts tumor progression patterns and survival in patients with atypical meningiomas following stereotactic radiosurgery.

PURPOSE: This study investigated whether Ki-67 labeling index (LI) correlated with clinical outcomes after SRS for atypical meningiomas. METHODS: This retrospective study examined 39 patients with atypical meningiomas who underwent SRS over a 10-year study period. Ki-67 LI was categorized into 3 groups: low (< 5%), intermediate (5%-10%), and high (> 10%). Local tumor control rates (LCRs), progression-free rates (PFRs), disease-specific survival (DSS) rates, and adverse radiation-induced events (AREs) were evaluated. RESULTS: The median follow-up periods were 26 months. SRS was performed at a median prescription dose of 18 Gy for tumors with a median Ki-67 LI of 9.6%. The 3-year LCRs were 100%, 74%, and 25% in the low, intermediate, and high LI groups, respectively (p = 0.011). The 3-year PFRs were 100%, 40%, and 0% in the low, intermediate, and high LI groups (p = 0.003). The 5-year DSS rates were 100%, 89%, and 50% in the low, intermediate, and high LI groups (p = 0.019). Multivariable Cox proportional hazard analysis showed a significant correlation of high LI with lower LCR (hazard ratio [HR], 3.92; 95% confidence interval [CI] 1.18-13.04, p = 0.026), lower PFR (HR 3.80; 95% CI 1.46-9.88, p = 0.006), and shorter DSS (HR 6.55; 95% CI 1.19-35.95, p = 0.031) compared with intermediate LI. The ARE rates were minimal (8%) in the entire group. CONCLUSION: Patients with high Ki-67 LI showed significantly more tumor progression and tumor-related death. Ki-67 LI might offer valuable predictive insights for the post-SRS management of atypical meningiomas.

Long-term outcomes of stereotactic radiosurgery for intracranial schwannoma in neurofibromatosis type 2: a genetic analysis perspective.

PURPOSE: Neurofibromatosis type 2 (NF2) is intractable because of multiple tumors involving the nervous system and is clinically diverse and genotype-dependent. Stereotactic radiosurgery (SRS) for NF2-associated schwannomas remains controversial. We aimed to investigate the association between radiosurgical outcomes and mutation types in NF2-associated schwannomas. METHODS: This single-institute retrospective study included consecutive NF2 patients with intracranial schwannomas treated with SRS. The patients' types of germline mutations ("Truncating," "Large deletion," "Splice site," "Missense," and "Mosaic") and Halliday's genetic severity scores were examined, and the associations with progression-free rate (PFR) and overall survival (OS) were analyzed. RESULTS: The study enrolled 14 patients with NF2 with 22 associated intracranial schwannomas (median follow-up, 102 months).　The PFRs in the entire cohort were 95% at 5 years and 90% at 10-20 years. The PFRs tended to be worse in patients with truncating mutation exons 2-13 than in those with other mutation types (91% at 5 years and 82% at 10-20 years vs. 100% at 10-20 years, P = 0.140). The OSs were 89% for patients aged 40 years and 74% for those aged 60 years in the entire cohort and significantly lower in genetic severity group 3 than in the other groups (100% vs. 50% for those aged 35 years; P = 0.016). CONCLUSION: SRS achieved excellent PFR for NF2-associated intracranial schwannomas in the mild (group 2A) and moderate (group 2B) groups. SRS necessitates careful consideration for the severe group (group 3), especially in cases with NF2 truncating mutation exons 2-13.

The importance of considering competing risks in recurrence analysis of intracranial meningioma.

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Safety evaluation of sinus patency after stereotactic radiosurgery for transverse-sigmoid sinus dural arteriovenous fistulas: implications of treatment options for patients with Borden type I fistulas.

OBJECTIVE: This study aimed to assess the efficacy and safety of stereotactic radiosurgery (SRS) in treating transverse-sigmoid sinus dural arteriovenous fistulas (TSS DAVFs), and to investigate post-SRS sinus patency, focusing on the risk factors associated with treated sinus occlusion. METHODS: Data from 34 patients treated with SRS between January 2006 and April 2023 were analyzed. Detailed angioarchitecture was confirmed using digital subtraction angiography before SRS. Angiography of the ipsilateral internal carotid artery and vertebral artery was performed to evaluate whether the involved side of the TSS was used for normal venous drainage. TSS stenosis was defined as sinus diameter < 50% of the normal proximal diameter. DAVF shunt obliteration, TSS occlusion, neurological status, and adverse events were also evaluated. RESULTS: Of the 34 patients, 21 had Borden type I and 14 had Borden type II DAVFs. The median age at SRS was 64 years (interquartile range 54-71 years), and the follow-up period was 31 months (interquartile range 15-94 months). Complete shunt obliteration was achieved in 24 (70.6%) patients. The cumulative 2-, 3-, and 5-year shunt obliteration rates were 49.6%, 71.2%, and 86.0%, respectively. Borden type I had higher obliteration rates (60.5%, 83.1%, and 94.4%, respectively) than Borden type II (41.7%, 51.4%, and 75.7%, respectively; p = 0.034). TSS occlusion occurred in 5 patients (14.7%). The cumulative 1-, 5-, and 10-year TSS occlusion rates were 2.9%, 8.3%, and 23.6%, respectively, across the entire cohort. All occlusions occurred exclusively in the sinuses that were not used for normal venous drainage. Cox proportional analyses revealed that TSS stenosis and the sinus not being used for normal venous drainage were significantly associated with a greater risk of TSS occlusion after SRS (HR 9.44, 95% CI 1.01-77.13; p = 0.049). CONCLUSIONS: SRS is effective and safe for TSS DAVF and results in favorable shunt obliteration, symptom improvement, and low complication rates. TSS occlusion after SRS is asymptomatic and is limited to sinuses that are not used for normal venous drainage.

Soft tissue Reconstruction Using Pedicled Trapezius Musculocutaneous Flap for Cranial Bone Flap Infection in the Occipital Region.

When managing cranial bone flap infections, infected bone flaps are typically removed and subsequently replaced with artificial bones 6 to 12 months after the inflammation subsides. However, defects in the occipital region pose challenges due to concerns regarding brain protection when patients lie in the supine position. Herein, the authors report the case of a 73-year-old woman with an occipital bone flap infection, which was successfully managed by reconstruction with a trapezius musculocutaneous flap immediately after removing the infected bone flap. One year and 2 months postoperatively, the wound had fully healed, and the patient remained symptom-free without any complications, such as sunken flap syndrome. Soft tissue reconstruction using pedicled trapezius musculocutaneous flap is a viable strategy for managing occipital bone flap infections. This flap ensures stable blood flow and requires minimal vascular manipulation, thereby reducing operation time as the patient does not need to change position.

[Preoperative 3D Microvascular Decompression Simulation].

Preoperative surgical simulation via three-dimensional fusion computer graphics models have been widely accepted as a legitimate means of securing the diagnosis and treatment effectiveness of neurovascular compression. The authors discussed three factors of surgical simulation as being 1. Knowing the anatomical relationship, 2. Knowing the desirable end result of surgical intervention, and 3. Knowing how to design surgical interventions to achieve such desirable end results. Satisfying each factor requires distinct functionality from the software used in the surgical simulation. As per the imaging study used to construct the multimodal computer graphic models, CT scan and MR are usually sufficient, although renal function-permitting contrast enhancement can be a feasible option for depicting minute vessels in particular. There are three major steps in building three-dimensional fusion computer graphics models:1. Image interpretation, 2. co-registration, and 3. Segmentation. Each step comprises an essential part that must be handled with care. The segmentation step is where rigorous technological advancement takes place, although classical techniques, such as the seeded region growing method or the multi-threshold method, are still practically important. Regarding surgical simulation after three-dimensional model construction, technical challenges concerning large deformations should be recognized to ensure non-nonsense surgical simulation.

Five-Year Stroke Risk and Its Predictors in Asymptomatic Moyamoya Disease: Asymptomatic Moyamoya Registry (AMORE).

BACKGROUND: Long-term outcomes are unknown in patients with asymptomatic moyamoya disease. In this report, we aimed to clarify their 5-year risk of stroke and its predictors. METHODS: We are conducting a multicenter, prospective cohort study (Asymptomatic Moyamoya Registry) in Japan. Participants were eligible if they were 20 to 70 years, had bilateral or unilateral moyamoya disease, experienced no episodes suggestive of TIA and stroke; and were functionally independent (modified Rankin Scale score 0-1). Demographic and radiological information was collected at enrollment. In this study, they are still followed up for 10 years. In this interim analysis, we defined the primary end point as a stroke occurring during a 5-year follow-up period. Independent predictors for stroke were also determined, using a stratification analysis method. RESULTS: Between 2012 and 2015, we enrolled 109 patients, of whom 103 patients with 182 involved hemispheres completed the 5-year follow-up. According to the findings on DSA and MRA, 143 hemispheres were judged as moyamoya disease and 39 hemispheres as questionable manifestations (isolated middle cerebral artery stenosis). The patients with questionable hemispheres were significantly older, more often male, and more frequently had hypertension than those with moyamoya hemisphere. Moyamoya hemispheres developed 7 strokes, including 6 hemorrhagic and 1 ischemic stroke, during the first 5 years. The annual risk of stroke was 1.4% per person, 0.8% per hemisphere, and 1.0% per moyamoya hemisphere. Independent predictor for stroke was Grade-2 choroidal anastomosis (hazard ratio, 5.05 [95% CI, 1.24-20.6]; P=0.023). Furthermore, microbleeds (hazard ratio, 4.89 [95% CI, 1.13-21.3]; P=0.0342) and Grade-2 choroidal anastomosis (hazard ratio, 7.05 [95% CI, 1.62-30.7]; P=0.0093) significantly predicted hemorrhagic stroke. No questionable hemispheres developed any stroke. CONCLUSIONS: The hemispheres with asymptomatic moyamoya disease may carry a 1.0% annual risk of stroke during the first 5 years, the majority of which are hemorrhagic stroke. Grade-2 choroidal anastomosis may predict stroke, and the microbleeds and Grade-2 choroidal anastomosis may carry the risk for hemorrhagic stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: UMIN000006640.

Somatic GJA4 gain-of-function mutation in orbital cavernous venous malformations.

Orbital cavernous venous malformation (OCVM) is a sporadic vascular anomaly of uncertain etiology characterized by abnormally dilated vascular channels. Here, we identify a somatic missense mutation, c.121G > T (p.Gly41Cys) in GJA4, which encodes a transmembrane protein that is a component of gap junctions and hemichannels in the vascular system, in OCVM tissues from 25/26 (96.2%) individuals with OCVM. GJA4 expression was detected in OCVM tissue including endothelial cells and the stroma, through immunohistochemistry. Within OCVM tissue, the mutation allele frequency was higher in endothelial cell-enriched fractions obtained using magnetic-activated cell sorting. Whole-cell voltage clamp analysis in Xenopus oocytes revealed that GJA4 c.121G > T (p.Gly41Cys) is a gain-of-function mutation that leads to the formation of a hyperactive hemichannel. Overexpression of the mutant protein in human umbilical vein endothelial cells led to a loss of cellular integrity, which was rescued by carbenoxolone, a non-specific gap junction/hemichannel inhibitor. Our data suggest that GJA4 c.121G > T (p.Gly41Cys) is a potential driver gene mutation for OCVM. We propose that hyperactive hemichannel plays a role in the development of this vascular phenotype.

Genetics of brain arteriovenous malformations and cerebral cavernous malformations.

Cerebrovascular malformations comprise abnormal development of cerebral vasculature. They can result in hemorrhagic stroke due to rupture of lesions as well as seizures and neurological defects. The most common forms of cerebrovascular malformations are brain arteriovenous malformations (bAVMs) and cerebral cavernous malformations (CCMs). They occur in both sporadic and inherited forms. Rapidly evolving molecular genetic methodologies have helped to identify causative or associated genes involved in genesis of bAVMs and CCMs. In this review, we highlight the current knowledge regarding the genetic basis of these malformations.

Lymphoproliferative disorder during temozolomide therapy; a representative case of a formidable complication and management challenges.

BACKGROUND: Lymphoproliferative disorder represents a heterogeneous clinicopathological spectrum characterized by uncontrolled proliferation of lymphocytes. Immunodeficiency is a major trigger of its development. While induction of immunodeficiency is a well-known adverse effect of temozolomide therapy, development of lymphoproliferative disorder following temozolomide therapy has not previously been described. CASE PRESENTATION: A patient with brainstem glioma developed constitutional symptoms, pancytopenia, splenomegaly and generalized lymphadenopathy during the 2nd cycle of maintenance therapy following induction therapy with temozolomide. Epstein-Barr virus-infected lymphocytes were observed histopathologically and "other iatrogenic immunodeficiency-associated lymphoproliferative disorder" (OIIA-LPD) was diagnosed. Although discontinuation of temozolomide led to rapid remission, relapse was observed 4 months later. CHOP chemotherapy was induced, resulting in secondary remission. Vigilant follow-up for another 14 months showed radiologically stable brainstem glioma and no further recurrence of OIIA-LPD. CONCLUSIONS: This is the first report documenting OIIA-LPD during temozolomide administration. Timely diagnosis of the disease and discontinuation of the causative agent were considered to be the management of choice. Close monitoring for relapse should be continued. Finding a balance between glioma management and controlling the remission of OIIA-LPD remains to be clarified.

Spatiotemporal target selection for intracranial neural decoding of abstract and concrete semantics.

Decoding the inner representation of a word meaning from human cortical activity is a substantial challenge in the development of speech brain-machine interfaces (BMIs). The semantic aspect of speech is a novel target of speech decoding that may enable versatile communication platforms for individuals with impaired speech ability; however, there is a paucity of electrocorticography studies in this field. We decoded the semantic representation of a word from single-trial cortical activity during an imageability-based property identification task that required participants to discriminate between the abstract and concrete words. Using high gamma activity in the language-dominant hemisphere, a support vector machine classifier could discriminate the 2-word categories with significantly high accuracy (73.1 ± 7.5%). Activities in specific time components from two brain regions were identified as significant predictors of abstract and concrete dichotomy. Classification using these feature components revealed that comparable prediction accuracy could be obtained based on a spatiotemporally targeted decoding approach. Our study demonstrated that mental representations of abstract and concrete word processing could be decoded from cortical high gamma activities, and the coverage of implanted electrodes and time window of analysis could be successfully minimized. Our findings lay the foundation for the future development of semantic-based speech BMIs.

Embryonal tumor with multilayered rosettes arising from the internal auditory canal of an adult: Illustrative case with molecular investigations.

Embryonal tumors with multilayered rosettes (ETMRs) are aggressive central nervous system (CNS) tumors that usually occur in young children. Here, we describe the first incidence of ETMR in an adult patient that also originated in the novel location of the internal auditory canal (IAC). The 36-year-old patient initially presented with unsteadiness, diplopia, and tinnitus. The tumor in the IAC was discovered on brain magnetic resonance imaging, and gross total resection was performed followed by pathological and molecular diagnosis. The patient received whole brain and spinal cord radiotherapy after an intracranial recurrence and adjuvant chemotherapy consisting of four cycles of ifosfamide, cisplatin, and etoposide. Progression was rapid; however, the patient survived for 22 months after diagnosis before succumbing to the disease. Molecular investigation revealed a DICER1 mutation at exon 25, and methylation classification categorized the tumor as ETMR, non-C19MC-altered. This case underscores the diverse possible presentations of ETMR, DICER1-mutated and the importance of molecular techniques to characterize and promptly treat atypical ETMR.

Stereotactic radiosurgery for recurrent pleomorphic adenoma of the lacrimal gland: a case report.

Lacrimal gland pleomorphic adenomas (LGPAs) are common, benign, and intraorbital tumours that cause exophthalmos, ptosis, and visual disturbances. The curative treatment for LGPAs is gross total resection, and radiotherapy is considered adjunctive for recurrence or an alternative for inoperable LGPAs. Stereotactic radiosurgery (SRS) can be used for precise delivery of high radiation doses to the tumour, crucial in the treatment of intra-and extracranial neoplasms. Here, we present a 95-year-old woman who had a rapidly growing, recurrent LGPA and was successfully treated with SRS. The tumour was controlled without any adverse events over 21 months following SRS. SRS is a potential alternative treatment for recurrent LGPA.

Indocyanine green illuminates the way to cut the tentorium in occipital transtentorial approach: technical note.

BACKGROUND AND IMPORTANCE: The occipital transtentorial approach is used to address lesions at the posterior incisural space or upper cerebellum. This approach is rarely used, making standardization of the surgical procedure challenging. Here we describe the effectiveness of indocyanine green (ICG) and dye markings before tentorial incision in charting a safe and bloodless surgical trajectory for improved manoeuvrability. CLINICAL PRESENTATION: The first case was a 40-year-old man with a residual pineal mass after chemoradiation therapy for pathologically-proven germinoma. Surgical resection was performed via left occipital craniotomy. Incision of the left cerebellar tentorium by a radiofrequency knife was preceded by visualization of the straight sinus and venous lake, which were marked with dye, enabling safe entry into the quadrigeminal cistern. Finally, total-resection of the mature teratoma was achieved. The second case was a 50-year-old man with an enhancing mass at the cerebellar vermis and left hemisphere. Left occipital craniotomy was followed by ICG administration, illuminating the straight sinus and a complex structure of dural venous channels, which were marked with dye. This visualization maximized the tentorial incision by carefully avoiding venous structures and widely exposed the upper cerebellum. Subtotal-resection of the tumor was achieved, with a diagnosis of glioblastoma. CONCLUSION: ICG administration and dye marking are feasible and useful methods for precise identification/visualization of venous structures. They enable maximization as well as safe and appropriate tentorial incision to provide a sufficient surgical corridor for the occipital transtentorial approach.

Hypertensive disorders of pregnancy in moyamoya disease: A single institution experience.

OBJECTIVE: The characteristics of pregnancy and delivery in patients with moyamoya disease (MMD) remain unclear. We retrospectively investigated perinatal outcomes in patients with MMD to evaluate the risks associated to this condition. MATERIALS AND METHODS: Clinical data of women with MMD who delivered at the University of Tokyo Hospital between 2000 and 2021 were collected. Maternal characteristics including genetic data, obstetric complications, method of delivery and anesthesia, neonatal outcomes, neurological events during pregnancy, delivery, and postpartum course, were reviewed. RESULTS: Thirteen pregnancies with MMD were identified. The median maternal age was 30 years. The initial clinical symptoms were identified as transient ischemic attack, infarction, and headache. Eight patients had a history of bypass surgery. The median gestational age at delivery was 37 weeks. DNA samples were collected from five patients, responsible for six pregnancies. Of these six cases, five had the RNF213 c.14429G > A (p.Arg4810Lys) heterozygous variant. Of the 13 pregnancies, seven had hypertensive disorder of pregnancy (HDP). Additionally, three of five pregnancy cases with RNF213 p.Arg4810Lys heterozygous variant presented with HDP. Nine patients underwent cesarean section, and four delivered vaginally with epidural anesthesia. One case of ischemic stroke was confirmed during the postpartum period. Regarding newborns, neither Apgar scores lower than 7 nor neonatal intensive care unit admissions were reported. CONCLUSIONS: This study suggests that the frequency of HDP is higher in patients with MMD compared to those with normal pregnancies. Strict blood pressure control should be performed in patients with MMD during pregnancy and postpartum period.

Reliability and sensitivity to altered hemodynamics measured with resting-state fMRI metrics: Comparison with 123I-IMP SPECT.

Blood oxygenation level-dependent (BOLD) contrast is sensitive to local hemodynamic changes and thus is applicable to imaging perfusion or vascular reactivity. However, knowledge about its measurement characteristics compared to reference standard perfusion imaging is limited. This study longitudinally evaluated perfusion in patients with steno-occlusive disease using resting-state functional MRI (rsfMRI) acquired before and within nine days of anterior circulation revascularization in patients with large cerebral artery steno-occlusive diseases. The reliability and sensitivity to longitudinal changes of rsfMRI temporal correlation (Rc) and time delay (TDc) relative to the cerebellar signal were examined voxel-wise in comparison with single-photon emission CT (SPECT) cerebral blood flow (CBF) using the within-subject standard deviation (Sw) and intraclass correlation coefficients (ICCs). For statistical comparisons, the standard deviation (SD) of longitudinal changes within the cerebellum, the number of voxels with significant changes in the left middle cerebral artery territory ipsilateral to surgery, and their average changes relative to the cerebellar SD were evaluated. The test-retest reliability of the fMRI metrics was also similarly evaluated using the human connectome project (HCP) healthy young adult dataset. The test-retest time interval was 31 ± 18 days. Test-retest reliability was significantly higher for SPECT (cerebellar SD: -2.59 ± 0.20) than for fMRI metrics (cerebellar SD: Rc, -2.34 ± 0.24, p = 0.04; TDc, -2.19 ± 0.21, p = 0.003). Sensitivity to postoperative changes, which was evaluated as the number of voxels, was significantly higher for fMRI TDc (8.78 ± 0.72) than for Rc (7.42 ± 1.48, p = 0.03) or SPECT CBF (6.88 ± 0.67, p < 0.001). The ratio between the average Rc, TDc, and SPECT CBF changes within the left MCA target region and cerebellar SD was also significantly higher for fMRI TDc (1.21 ± 0.79) than Rc (0.48 ± 0.94, p = 0.006) or SPECT CBF (0.23 ± 0.57, p = 0.001). The measurement variability of time delay was also larger than that of temporal correlation in HCP data within the cerebellum (t = -8.7, p < 0.001) or in the whole-brain (t = -27.4, p < 0.001) gray matter. These data suggest that fMRI time delay is more sensitive to the hemodynamic changes than SPECT CBF, although the reliability is lower. The implication for fMRI connectivity studies is that temporal correlation can be significantly decreased due to altered hemodynamics, even in cases with normal CBF.

Arterial Transit Time-Based Multidelay Combination Strategy Improves Arterial Spin Labeling Cerebral Blood Flow Measurement Accuracy in Severe Steno-Occlusive Diseases.

BACKGROUND: Although perfusion imaging plays a key role in the management of steno-occlusive diseases, the clinical usefulness of arterial spin labeling (ASL) is limited by technical issues. PURPOSE: To examine the effect of arterial transit time (ATT) prolongation on cerebral blood flow (CBF) measurement accuracy and identify the best CBF measurement protocol for steno-occlusive diseases. STUDY TYPE: Prospective. POPULATION: Moyamoya (n = 10) and atherosclerotic diseases (n = 8). FIELD STRENGTH/SEQUENCE: A 3.0T/3DT1 -weighted and ASL. ASSESSMENT: Hadamard-encoded multidelay ASL scans with/without vessel suppression (VS) and single-delay ASL scans with long-label duration (LD) and long postlabeling delay (PLD), referred to as long-label long-delay (LLLD), were acquired. CBF measurement accuracy and its ATT dependency, measured as the correlation between the relative CBF measurement difference (ASL-single-photon emission computed tomography [SPECT]) and ATT, were compared among 1) Combo (incorporating multidelay and LLLD data based on ATT), 2) standard (LD/PLD = 1333/2333 msec), and 3) LLLD (LD/PLD = 4000/4000 msec) protocols, using whole-brain voxel-wise correlation with reference standard SPECT CBF. The effect of VS on CBF measurement accuracy was also assessed. STATISTICAL TESTS: Pearson's correlation coefficient, repeated-measures analysis of variance, t-test. P< 0.05 was considered significant. RESULTS: Pearson's correlation coefficients between ASL and SPECT CBF measurements were as follows: Combo = 0.55 ± 0.09; standard = 0.52 ± 0.12; LLLD = 0.41 ± 0.10. CBF measurement was least accurate in LLLD and most accurate in Combo. VS significantly improved overall CBF measurement accuracy in the standard protocol and in moyamoya patients for the Combo. ATT dependency analysis revealed that, compared with Combo, the standard and LLLD protocols showed significantly lower and negative and significantly higher and positive correlations, respectively (standard = -0.12 ± 0.04, Combo = -0.04 ± 0.03, LLLD = 0.17 ± 0.03). DATA CONCLUSION: By using ATT-corrected CBF derived from LD/PLD = 1333/2333 msec as a base and by compensating underestimation in delayed regions using multidelay scans, the ATT-based Combo strategy improves CBF measurement accuracy compared with single-delay protocols in severe steno-occlusive diseases. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.