Assessment of cerebral perfusion in moyamoya disease with dynamic pseudo-continuous arterial spin labeling using a variable repetition time scheme with optimized background suppression.

PURPOSE: Accurate assessment of cerebral perfusion in moyamoya disease is necessary to determine the indication for treatment. We aimed to investigate the usefulness of dynamic PCASL using a variable TR scheme with optimized background suppression in the evaluation of cerebral perfusion in moyamoya disease. METHODS: We retrospectively analyzed the images of 24 patients (6 men and 18 women, mean age 31.4 ± 18.2 years) with moyamoya disease; each of whom was imaged with both dynamic PCASL using the variable-TR scheme and 123IMP SPECT with acetazolamide challenge. ASL dynamic data at 10 phases are acquired by changing the LD and PLD. The background suppression timing was optimized for each phase. CBF and ATT were measured with ASL, and CBF and CVR to an acetazolamide challenge were measured with SPECT. RESULTS: A significant moderate correlation was found between the CBF measured by dynamic PCASL and that by SPECT (r = 0.53, P < 0.001). The CBF measured by dynamic PCASL (52.5 ± 13.3 ml/100 mg/min) was significantly higher than that measured by SPECT (43.0 ± 12.6 ml/100 mg/min, P < 0.001). The ATT measured by dynamic PCASL showed a significant correlation with the CVR measured by SPECT (r = 0.44, P < 0.001). ATT was significantly longer in areas where the CVR was impaired (CVR < 18.4%, ATT = 1812 ± 353 ms) than in areas where it was preserved (CVR > 18.4%, ATT = 1301 ± 437 ms, P < 0.001). The ROC analysis showed a moderate accuracy (AUC = 0.807, sensitivity = 87.7%, specificity = 70.4%) when the cutoff value of ATT was set at 1518 ms. CONCLUSION: Dynamic PCASL using this scheme was found to be useful for assessing cerebral perfusion in moyamoya disease.

Different hemodynamics of basal ganglia between moyamoya and non-moyamoya diseases using intravoxel incoherent motion imaging and single-photon emission computed tomography.

BACKGROUND: Moyamoya disease (MMD) and non-MMD have different pathogenesis, clinical presentation, and treatment policy. PURPOSE: To identify differences in hemodynamics between MMD and non-MMD using intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). MATERIAL AND METHODS: Patients who had undergone 99mTc-ECD or 123I-IMP SPECT, and IVIM imaging were retrospectively studied. IVIM imaging was acquired using six different b-values. Cerebral blood flow ratio (CBFR) in the basal ganglia was calculated using a standardized volume-of-interest template. The cerebellum was used as a reference region. IVIM perfusion fraction (f) was obtained using a two-step fitting algorithm. Elliptical regions of interest were placed in bilateral basal ganglia on the IVIM f map. Patients were classified into MMD and non-MMD groups. The correlation between CBFR and mean IVIM f (fmean) in the basal ganglia was evaluated using Spearman's rank correlation coefficient. RESULTS: In total, 20 patients with MMD and 28 non-MMD patients were analyzed. No significant differences in fmean were observed among MMD, affected hemisphere with non-MMD (non-MMDaff), and unaffected hemispheres with non-MMD (non-MMDunaff). A negative correlation was seen between fmean and CBFR in the MMD group (r = -0.40, P = 0.0108), but not in the non-MMD group (non-MMDaff, r = 0.07, P = 0.69; non-MMDunaff, r = -0.22, P = 0.29). No significant differences were found among MMD and non-MMD patients, irrespective of SPECT tracers. CONCLUSION: The combination of IVIM MRI and SPECT appears to allow non-invasive identification of differences in hemodynamics between MMD and non-MMD.

[Unruptured Fronto-Orbital Artery Aneurysm Anomalously Originating from the Proximal Segment of the Anterior Cerebral Artery(A1)Concurrent with Tuberculum Sellae Meningioma:A Case Report].

We report a case of an unruptured aneurysm arising from the bifurcation of the fronto-orbital artery originating from the proximal segment of the left anterior cerebral artery(A1)concurrent with a tuberculum sellae meningioma. A 46-year-old woman presented with a right visual disturbance and left temporal hemianopsia. Preoperative neuroradiological examination showed a heterogeneously enhanced extra-axial suprasellar tumor expanding to the right optic canal and 3-mm diameter aneurysm arising from the bifurcation of the fronto-orbital artery originating from the proximal segment of the left anterior cerebral artery(A1). She underwent total removal of the tumor and neck clipping of the aneurysm via a right pterional approach without any additional deficits. Postoperative MRI and 3D CTA showed total tumor removal and complete obliteration of the aneurysm. The patient was discharged 21 days after surgery without new or worsened postoperative neurological deficits. Cerebral aneurysm concurrent with meningioma is extremely rare. Preoperative diagnosis and appropriate assessment of both the meningioma and unruptured aneurysm are warranted to prevent severe complications.

Detection of proneural/mesenchymal marker expression in glioblastoma: temporospatial dynamics and association with chromatin-modifying gene expression.

Proneural and mesenchymal are two subtypes of glioblastoma identified by gene expression profiling. In this study, the primary aim was to detect markers to develop a clinically applicable method for distinguishing proneural and mesenchymal glioblastoma. The secondary aims were to investigate the temporospatial dynamics of these markers and to explore the association between these markers and the expression of chromatin-modifying genes. One hundred thirty-three glioma samples (grade II: 14 samples, grade III: 18, grade IV: 101) were analyzed. We quantified the expression of 6 signature genes associated with proneural and mesenchymal glioblastoma by quantitative reverse transcription-polymerase chain reaction. We assigned proneural (PN) and mesenchymal (MES) scores based on the average of the 6 markers and calculated a predominant metagene (P-M) score by subtracting the MES from the PN score. We used these scores to analyze correlations with malignant transformation, tumor recurrence, tumor heterogeneity, chromatin-modifying gene expression, and HDAC7 expression. The MES score positively correlated with tumor grade, whereas the PN score did not. The P-M score was able to distinguish the proneural and mesenchymal subtypes. It was decreased in cases of tumor recurrence and malignant transformation and showed variability within a tumor, suggesting intratumoral heterogeneity. The PN score correlated with the expression of multiple histone-modifying genes, whereas the MES score was associated only with HDAC7 expression. Thus, we demonstrated a simple and straightforward method of quantifying proneural/mesenchymal markers in glioblastoma. Of note, HDAC7 expression might be a novel therapeutic target in glioblastoma treatment.

A case of intracranial solitary fibrous tumor/hemangiopericytoma with dedifferentiated component.

We report the case of a 51-year-old Japanese man with an intracranial dedifferentiated solitary fibrous tumor/hemangiopericytoma (SFT/HPC) identified morphologically and immunohistochemically, comprised of a typical SFT/HPC with a high-grade pleomorphic component. NAB2-STAT6 fusion transcripts were detected by reverse transcriptase polymerase chain reaction in both the conventional and high-grade components. The tumor cells in both components showed the nuclear expression of STAT6 protein, indicating the diagnostic value of these examinations. Intracranial dedifferentiated SFT/HPC is a very rare but important differential diagnosis in intracranial pleomorphic tumors.

Mechanisms underlying increased vascular smooth muscle contractility in the rabbit basilar artery following subarachnoid hemorrhage.

Increased vascular contractility plays an important role in the development of cerebral vasospasm following subarachnoid hemorrhage (SAH). Here, we summarize our current knowledge regarding molecular mechanisms that contribute to increased smooth muscle contractility of rabbit basilar artery following SAH. Our studies demonstrated that upregulation of receptor expression, impairment of feedback regulation of receptor activity, and enhancement of myofilament Ca²âº sensitization might lead to increased smooth muscle contractility following SAH.

Executive function and diffusion in frontal white matter of adults with moyamoya disease.

BACKGROUND: Cognitive impairment is a frequent complication of moyamoya disease (MMD) in adults. Chronic hypoperfusion in frontal lobes can lead to subtle brain injury, resulting in cognitive dysfunctions. Apparent diffusion coefficient (ADC) in normal-appearing white matter on conventional magnetic resonance imaging correlates with cerebral hemodynamics in the frontal lobe. OBJECTIVE: The purpose of this study was to examine the relationship of ADC with executive function in patients with MMD. METHODS: Thirty-one patients (25 women and 6 men; mean age, 32.6 ± 10.4 years) were included in this study. Executive function was evaluated by the Frontal Assessment Battery (FAB) at 21.5 ± 7.5 years after disease onset. ADC was measured in the normal-appearing frontal white matter. RESULTS: ADC was statistically related to the occurrence of executive dysfunction in multivariate analysis (P = .0179). Total FAB score and ADC were negatively correlated (r(2) = .22; P = .0072; Spearman correlation coefficient, -.41; P = .024). Elevated ADC predicted executive dysfunction (area under the receiver operating characteristic curve, .73; 95% confidence interval, .55-.91; P = .029). CONCLUSIONS: The association of ADC with executive function might suggest that ADC is useful in screening for executive dysfunction during follow-up in the outpatient setting.

Intellectual function and memory in children with moyamoya disease: relationship between Wechsler Intelligence Scale and Benton Visual Retention Test scores and regional cerebral blood flow.

OBJECTIVE: Intellectual function declines in about 30% of children with moyamoya disease (MMD). Memory function underpins higher order brain function, but the relationship between intellectual function and memory in pediatric MMD patients has not been well studied. This study aimed to investigate correlations between scores on the Wechsler Intelligence Scale for Children (WISC) and the Benton Visual Retention Test (BVRT), a visual memory test that can be administered to children, in children with MMD. Relationships between intellectual function or memory and regional cerebral blood flow (rCBF) have also not been well clarified in pediatric MMD patients. The authors also investigated associations between WISC or BVRT scores and rCBF in various brain regions. METHODS: WISC and BVRT scores and rCBF were assessed in 17 children with ischemic-onset MMD before revascularization. Single-photon emission CT with 123I-iodoamphetamine was used to measure rCBF. Relationships between WISC and BVRT scores were evaluated using Spearman's correlation coefficient and multivariate linear regression analysis. Cutoff values were identified for BVRT scores. Sensitivity and specificity were calculated to predict full-scale intelligence quotient (FSIQ) > 85 or ≤ 85. Associations between rCBF and WISC or BVRT scores were evaluated using linear regression analysis. RESULTS: BVRT scores were significantly correlated with FSIQ and scores on the Working Memory Index (WMI), Processing Speed Index, and Verbal Comprehension Index (VCI)/Verbal Intelligence Quotient (VIQ) of WISC. Multivariate linear regression revealed that number correct score and number of errors score of BVRT were associated with FSIQ. As cutoff values, a number correct score of 5 and a number of errors score of 8 offered the most reliable predictors of FSIQ > 85 and ≤ 85, respectively. FSIQ correlated positively with rCBF in the right and left hemispheres, right and left ganglia, right and left thalamus, right and left cerebellum, right middle cerebral artery (MCA) territory, pons, and vermis. WMI score was positively associated with rCBF in the right hemisphere, right anterior cerebral artery territory, right MCA territory, right basal ganglia, right and left thalamus, right and left cerebellum, pons, and vermis. CONCLUSIONS: BVRT score correlated well with WISC index scores, suggesting that BVRT may be helpful in screening for intellectual impairments in children with MMD. In the MCA territory, basal ganglia, thalamus, cerebellum, pons, and vermis, rCBF associated well with WISC index scores, suggesting that reduced rCBF in relevant brain regions may influence intellectual function.

Advantages of 3D High-Resolution Vessel Wall Imaging in a Patient With Blood Blister-Like Aneurysm: A Case Report and Literature Review.

Blood blister-like aneurysms (BBAs) are rare and challenging intracranial aneurysms. They pose significant diagnostic and surgical risks due to their delicate walls. Accounting for a small percentage of intracranial aneurysms, BBAs are pathologically pseudoaneurysms, often resulting from arterial dissection, with a high tendency to rupture. This report underscores the critical nature of BBAs by reviewing a case in which subarachnoid hemorrhage caused by a BBA rupture was difficult to diagnose with conventional imaging. We highlight the efficacy of three-dimensional (3D) high-resolution vessel wall imaging (VWI) in discerning the subtle vascular abnormality of BBAs. The integration of the black-blood imaging technique within VWI provides superior contrast between the aneurysm and surrounding tissues, facilitating clearer visualization of the aneurysmal wall. The use of 3D T1-weighted imaging provides intricate details of the vessel wall including its contrast enhancement, which is crucial for a comprehensive assessment of a ruptured aneurysm. This case is consistent with the existing literature, supporting the role of VWI in the identification of ruptured BBAs, an area with limited but growing information on its diagnostic value. VWI is precise and accurate in the preoperative diagnosis of BBAs, emphasizing its potential to improve patient management and outcomes, especially in conditions with high risks of morbidity and mortality.

Brain volume measured by synthetic magnetic resonance imaging in adult moyamoya disease correlates with cerebral blood flow and brain function.

Moyamoya disease (MMD) is characterized by progressive arterial occlusion, causing chronic hemodynamic impairment, which can reduce brain volume. A novel quantitative technique, synthetic magnetic resonance imaging (SyMRI), can evaluate brain volume. This study aimed to investigate whether brain volume measured with SyMRI correlated with cerebral blood flow (CBF) and brain function in adult MMD. In this retrospective study, 18 adult patients with MMD were included. CBF was measured using iodine-123-N-isopropyl-p-iodoamphetamine single photon emission computed tomography. Cerebrovascular reactivity (CVR) to acetazolamide challenge was also evaluated. Brain function was measured using the Wechsler Adult Intelligence Scales (WAIS)-III/IV and the WAIS-R tests. Gray matter (GM), white matter, and myelin-correlated volumes were evaluated in six areas. Resting CBF was positively correlated with GM fractions in the right anterior cerebral arterial and right middle cerebral arterial (MCA) territories. CVR was positively correlated with GM fraction in the right posterior cerebral arterial (PCA) territory. Full-Scale Intelligence Quotient and Verbal Comprehension Index scores were marginally positively correlated with GM fractions in the left PCA territory. Processing Speed Index score was marginally positively correlated with GM fraction in the right MCA territory. The SyMRI-measured territorial GM fraction correlated with CBF and brain function in patients with MMD.

Liquid Biopsy for Glioma Using Cell-Free DNA in Cerebrospinal Fluid.

Glioma is one of the most common primary central nervous system (CNS) tumors, and its molecular diagnosis is crucial. However, surgical resection or biopsy is risky when the tumor is located deep in the brain or brainstem. In such cases, a minimally invasive approach to liquid biopsy is beneficial. Cell-free DNA (cfDNA), which directly reflects tumor-specific genetic changes, has attracted attention as a target for liquid biopsy, and blood-based cfDNA monitoring has been demonstrated for other extra-cranial cancers. However, it is still challenging to fully detect CNS tumors derived from cfDNA in the blood, including gliomas, because of the unique structure of the blood-brain barrier. Alternatively, cerebrospinal fluid (CSF) is an ideal source of cfDNA and is expected to contribute significantly to the liquid biopsy of gliomas. Several successful studies have been conducted to detect tumor-specific genetic alterations in cfDNA from CSF using digital PCR and/or next-generation sequencing. This review summarizes the current status of CSF-based cfDNA-targeted liquid biopsy for gliomas. It highlights how the approaches differ from liquid biopsies of other extra-cranial cancers and discusses the current issues and prospects.

Hemizygous deletion of cyclin-dependent kinase inhibitor 2A/B with p16 immuno-negative and methylthioadenosine phosphorylase retention predicts poor prognosis in IDH-mutant adult glioma.

Background: Homozygous deletion of the tumor suppression genes cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) is a strong adverse prognostic factor in IDH-mutant gliomas, particularly astrocytoma. However, the impact of hemizygous deletion of CDKN2A/B is unknown. Furthermore, the influence of CDKN2A/B status in IDH-mutant and 1p/19q-codeleted oligodendroglioma remains controversial. We examined the impact of CDKN2A/B status classification, including hemizygous deletions, on the prognosis of IDH-mutant gliomas. Methods: We enrolled 101 adults with IDH-mutant glioma between December 2002 and November 2021. CDKN2A/B deletion was evaluated with multiplex ligation-dependent probe amplification (MLPA). Immunohistochemical analysis of p16/MTAP and promoter methylation analysis with methylation-specific MLPA was performed for cases with CDKN2A/B deletion. Kaplan - Meier plots and Cox proportion hazards model analyses were performed to evaluate the impact on overall (OS) and progression-free survival. Results: Of 101 cases, 12 and 4 were classified as hemizygous and homozygous deletion, respectively. Immunohistochemistry revealed p16-negative and MTAP retention in cases with hemizygous deletion, whereas homozygous deletions had p16-negative and MTAP loss. In astrocytoma, OS was shorter in the order of homozygous deletion, hemizygous deletion, and copy-neutral groups (median OS: 38.5, 59.5, and 93.1 months, respectively). Multivariate analysis revealed hazard ratios of 9.30 (P = .0191) and 2.44 (P = .0943) for homozygous and hemizygous deletions, respectively. Conclusions: CDKN2A/B hemizygous deletions exerted a negative impact on OS in astrocytoma. Immunohistochemistry of p16/MTAP can be utilized to validate hemizygous or homozygous deletions in combination with conventional molecular diagnosis.

Pediatric glioblastoma with oligodendroglioma component: aggressive clinical phenotype with distinct molecular characteristics.

The 2007 World Health Organization classification defined a new variant of glioblastoma (GBM) containing oligodendroglioma foci as GBM with an oligodendroglioma component (GBMO), which shows a favorable clinical outcome compared with "classic" GBM. However, all of the reported cases of GBMO have been adult cases, with no previous reports of pediatric cases. In this report, we demonstrated molecular characteristics of a pediatric GBMO case, showing aggressive clinical behavior with 8-month overall survival. The case showed neither isocitrate dehydrogenase 1/2 genes (IDH1/2) mutation nor 1p/19q co-deletion, a hallmark of oligodendroglioal tumors. In addition, microsatellite instability, leading to the putative mechanism of temozolomide (TMZ) resistance, was frequently detected. Molecular genetic analysis may provide critical prognostic and therapeutic insights, especially for the pediatric glioma containing oligodendroglioma components.

Usefulness of three-dimensional T1-weighted spoiled gradient-recalled echo and three-dimensional heavily T2-weighted images in preoperative evaluation of spinal dysraphism.

PURPOSE: The aim of this study was to evaluate the usefulness of three-dimensional T1-weighted spoiled gradient-recalled echo (3D T1-GRE) images for the preoperative anatomical evaluation of lumbosacral lipoma, thick filum terminale, and myelomeningocele as a means of compensating for the drawbacks of 3D heavily T2-weighted (3D hT2-W) images. METHODS: Nine patients with lumbosacral lipomas, one patient with tight filum terminale, and five patients with myelomeningoceles were included in this study. 3D T1-GRE images were compared with 3D hT2-W images or conventional magnetic resonance images in terms of delineation of lipomas and other structures in the patients with lipomas and tight filum terminale. For patients with myelomeningoceles, 3D T1-GRE images were compared with 3D hT2-W images in terms of artifacts in the cerebrospinal fluid (CSF) space. RESULTS: The 3D T1-GRE images demonstrated lipomas with good contrast to the spinal cord and CSF space and more clearly delineated the anatomical relationship between lipomas and these structures than did the 3D hT2-W images. The 3D T1-GRE images delineated dural defects through which extradural lipomas penetrated into the intradural space. The 3D T1-GRE images also demonstrated the presence or absence of lipomas in the filum terminale and the absence of artifact in the myelomeningoceles. Furthermore, they were useful for differentiating artifacts observed on the 3D hT2-W images from nerve elements. CONCLUSIONS: The complementary use of 3D T1-GRE and 3D hT2-W images may compensate for the drawbacks of 3D hT2-W images and may eventually improve lesion visualization and surgical decision making.

Dorsal location of the cochlear nerve on vestibular schwannoma: preoperative evaluation, frequency, and functional outcome.

The cochlear nerve is most commonly located on the caudoventral portion of the capsule of vestibular schwannomas and rarely on the dorsal portion. In such a condition, total removal of the tumor without cochlear nerve dysfunction is extremely difficult. The purpose of our study was to identify the frequency of this anatomical condition and the status of postoperative cochlear nerve function; we also discuss the preoperative radiological findings. The study involved 114 patients with unilateral vestibular schwannomas operated on via a retrosigmoid (lateral suboccipital) approach. Locations of the cochlear nerve on the tumor capsule were ventral, dorsal, caudal, and rostral. Ventral and dorsal locations were further subdivided into rostral, middle, and caudal third of the tumor capsule. The postoperative cochlear nerve function and preoperative magnetic resonance (MR) findings were reviewed retrospectively. In 56 patients that had useful preoperative hearing, useful hearing was retained in 50.0% (28 of 56) of patients after surgery. The cochlear nerve was located on the dorsal portion of the tumor capsule in four patients (3.5%), and useful hearing was preserved in only one of these patients (25%) in whom the tumor had been partially resected. This tumor-nerve anatomical relationship was identified in all tumors of <2 cm at preoperative MR cisternography. MR cisternography has the potential to identify the tumor-nerve anatomical relationship, especially in small-sized tumors that usually require therapeutic intervention that ensures hearing preservation. Hence, careful evaluation of the preoperative MR cisternography is important in deciding the therapeutic indications.

Surgical techniques for the dissection of encased perforators in giant clinoidal meningiomas.

BACKGROUND: Surgical treatment of giant clinoidal meningiomas remains a challenging task for neurosurgeons. Here, we present details of the surgical techniques for the dissection of encased perforators. METHODS: The dissection of encased perforators is summarized as follows: (1) split the tumor above the encased arteries and perforators; (2) find the entrance and exit points of the perforators, and estimate the running course of the perforators within the tumor; (3) dissect and expose the perforators along the estimated line. CONCLUSIONS: The surgical techniques described in this article will aid in achieving maximum tumor resection while preserving encased perforators.

Posterior transjugular and transcervical approach for glomus tumours within the head and neck.

Glomus tumours within the head and neck are highly vascular in nature and are surrounded by vital neurovascular structures. The aim of this study is to review the step-by-step surgical techniques for a posterior transjugular approach and transcervical approach and to clarify the advantages of these approaches in the treatment of glomus tumours within the head and neck. The advantage of these approaches is that a wide operative field from the jugular bulb to the cervical portion can be obtained. In addition, the bloodless operative field that is achieved by the preoperative embolisation appeared to contribute to reducing the risk of cranial nerve injury.

Preoperative evaluation and surgical strategies for craniocervical junction dural arteriovenous fistula with multiple feeders: case report and review of the literature.

Craniocervical junction dural arteriovenous fistula (CCJDAVF) fed by bilateral vertebral arteries (VAs) is extremely rare. We report a case of a 63-year-old man presenting with progressive myelopathy caused by a CCJDAVF, which was fed by bilateral VAs and occipital and ascending pharyngeal arteries with multiple shunting points and that drained into intracranial sinus and spinal veins. The dural arteriovenous fistula (DAVF) was successfully treated surgically using stepwise indocyanine green (ICG) videoangiography. After surgery, the DAVF disappeared and myelopathy was markedly improved. We show detailed preoperative images and intraoperative findings of this rare DAVF and emphasize the importance of selective angiography for preoperative evaluation of feeding arteries and the usefulness of intraoperative ICG videoangiography for both identification of the fistula and confirmation of its obliteration.

Hemifacial Spasm Caused by Vascular Compression of the Anterior Inferior Cerebellar Artery-Posterior Inferior Cerebellar Artery Common Trunk Anomaly at the Cisternal Portion of the Facial Nerve: A Case Report.

W report the first case of hemifacial spasm (HFS) caused by vascular compression of the anterior inferior cerebellar artery (AICA)-posterior inferior cerebellar artery (PICA) common trunk anomaly at the cisternal portion of cranial nerve VII (CN VII). A 71-year-old female with a typical right HFS was admitted to our hospital. As per her magnetic resonance (MR) imaging results, no offending arteries were noted around the CN VII root exit zone (REZ). Computed tomography angiography revealed an AICA-PICA common trunk anomaly with a dominant PICA, with the rostral branch of the AICA-PICA common trunk anomaly compressing the CN VII at the cisternal portion. The patient underwent microvascular decompression (MVD), and the HFS disappeared after surgery. The amplitude of the abnormal muscle responses (AMR) disappeared immediately after complete transposition of the offending artery. However, the patient experienced mild transient facial palsy 3 days after MVD which was eventually resolved with the administration of vitamin B12. No HFS recurrence was observed during the 1-year follow-up period. The AICA-PICA common trunk anomaly has been found to cause HFS as it compressed the CN VII at the cisternal portion, and not at the REZ. AMR monitoring might be helpful for cases where the unusual vessel particularly compresses the CN VII.