Aqueductal Cerebrospinal Fluid Stroke Volume Flow in a Rodent Model of Chronic Communicating Hydrocephalus: Establishing a Homogeneous Study Population for Cerebrospinal Fluid Dynamics Exploration.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a cause of dementia that can be reversed when treated timely with cerebrospinal fluid (CSF) diversion. Understanding CSF dynamics throughout the development of hydrocephalus is crucial to identify prognostic markers to estimate benefit/risk to shunts. OBJECTIVE: To explore the cerebral aqueduct CSF flow dynamics with phase-contrast magnetic resonance imaging (MRI) in a novel rodent model of adult chronic communicating hydrocephalus. METHODS: Kaolin was injected into the subarachnoid space at the convexities in Sprague-Dawley adult rats. 11.7-T Bruker MRI was used to acquire T2-weighted images for anatomic identification and phase-contrast MRI at the cerebral aqueduct. Aqueductal stroke volume (ASV) results were compared with the ventricular volume (VV) at 15, 60, 90, and 120 days. RESULTS: Significant ventricular enlargement was found in kaolin-injected animals at all times (P < 0.001). ASV differed between cases and controls/shams at every time point (P = 0.004, 0.001, 0.001, and <0.001 at 15, 60, 90, and 120 days, respectively). After correlation between the ASV and the VV, there was a significant correlation at 15 (P = 0.015), 60 (P = 0.001), 90 (P < 0.001), and 120 days. Moreover, there was a significant positive correlation between the VV expansion and the aqueductal CSF stroke between 15 and 60 days. CONCLUSIONS: An initial active phase of rapid ventricular enlargement shows a strong correlation between the expansion of the VV and the increment in the ASV during the first 60 days, followed by a second phase with less ventricular enlargement and heterogeneous behavior in the ASV. Further correlation with complementary data from intracranial pressure and histologic/microstructural brain parenchyma assessments are needed to better understand the ASV variations after 60 days.

Ventricular Volume Dynamics During the Development of Adult Chronic Communicating Hydrocephalus in a Rodent Model.

INTRODUCTION: The pathophysiology of normal-pressure hydrocephalus and the correlation with its symptomatology is not well understood. OBJECTIVE: To monitor and evaluate the enlargement patterns of the ventricular system for each ventricle and its correlation with the presenting symptoms. METHODS: Bilateral kaolin injection into the subarachnoid space overlying the cranial convexities was done in 18 adult rats. Magnetic resonance imaging was performed on an 11.7-T scanner 15, 60, 90, and 120 days after injection. Volumes of the ventricular system were measured for each ventricle and correlated with biweekly behavioral findings. RESULTS: There was a progressive increase in the ventricular volume for the lateral ventricles since day 15 in the kaolin-injected animals. There was a nonsignificant trend in volume growth for the third ventricle, but its enlargement was synchronous with the lateral ventricles. No significant change for the fourth ventricle. No symptoms were detected in the first 60 days. Association was found between the ventricular volume and locomotor changes. In addition, the odds of locomotor symptoms increased by 3% for every additional cubic millimeter of volume in the left (P < 0.001) and right (P = 0.023) ventricles, and for the total magnetic resonance imaging volume by 1% (P = 0.013). CONCLUSIONS: Expansion of the lateral ventricles maintained similar proportions over time, accompanied by a synchronous third ventricular expansion with less proportion and a nonsignificant fourth enlargement. Lateral ventricles enlarged most in those animals that were to develop late locomotor deterioration. Further research using this animal model combined with different radiologic imaging techniques, such as diffusion tensor imaging and perfusion studies, is recommended.

Correction to: Correlation of CSF flow using phase-contrast MRI with ventriculomegaly and CSF opening pressure in mucopolysaccharidoses.

After publication of the article [1], it has been brought to our attention that the full funding acknowledgement is missing from the original article.

Correlation of CSF flow using phase-contrast MRI with ventriculomegaly and CSF opening pressure in mucopolysaccharidoses.

BACKGROUND: Very little is known about the incidence and prevalence of hydrocephalus in patients with mucopolysaccharidoses (MPS). The biggest challenge is to distinguish communicating hydrocephalus from ventricular dilatation secondary to brain atrophy, because both conditions share common clinical and neuroradiological features. The main purpose of this study is to assess the relationship between ventriculomegaly, brain and cerebrospinal fluid (CSF) volumes, aqueductal and cervical CSF flows, and CSF opening pressure in MPS patients, and to provide potential biomarkers for abnormal CSF circulation. METHODS: Forty-three MPS patients (12 MPS I, 15 MPS II, 5 MPS III, 9 MPS IV A and 2 MPS VI) performed clinical and developmental tests, and T1, T2, FLAIR and phase-contrast magnetic resonance imaging (MRI) followed by a lumbar puncture with the CSF opening pressure assessment. For the analysis of MRI variables, we measured the brain and CSF volumes, white matter (WM) lesion load, Evans' index, third ventricle width, callosal angle, dilated perivascular spaces (PVS), craniocervical junction stenosis, aqueductal and cervical CSF stroke volumes, and CSF glycosaminoglycans concentration. RESULTS: All the scores used to assess the supratentorial ventricles enlargement and the ventricular CSF volume presented a moderate correlation with the aqueductal CSF stroke volume (ACSV). The CSF opening pressure did not correlate either with the three measures of ventriculomegaly, or the ventricular CSF volume, or with the ACSV. Dilated PVS showed a significant association with the ventriculomegaly, ventricular CSF volume and elevated ACSV. CONCLUSIONS: In MPS patients ventriculomegaly is associated with a severe phenotype, increased cognitive decline, WM lesion severity and enlarged PVS. The authors have shown that there are associations between CSF flow measurements and measurements related to CSF volumetrics. There was also an association of volumetric measurements with the degree of dilated PVS.

Arterial hypertension impact on cerebral blood flow in patients with Alzheimer's disease / Impacto da hipertensão arterial sobre fluxo de sangue cerebral em pacientes com a doença de Alzheimer

Background: Studies show the potential deterioration of brain vascularization and probable involvement of hypertension in Alzheimer disease (AD). Objective: The objective was to evaluate the potential impact of hypertension on cerebral vascular flows in a sample of Alzheimer's patients. Methods: 19 patients with AD, including 10 with hypertension (aHT+) and 9 without hypertension (aHT-) were recruited. They underwent clinical evaluation and phase-contrast MRI protocol for flow assessment. Cerebral arterial flow distributions were evaluated using kurtosis and skewness indices at the intracranial and extracranial levels. Results: No significant differences were found in the mean arterial flow, pulse flow and kurtosis between the levels in the AD aHT+ population. There was a significant difference in skewness between extra- and intracranial levels (p = 0.01). No significant differences were found in the mean arterial flow between the levels in the AD aHT- population. A significant difference was observed in the pulse flow (p = 0.03), kurtosis (p = 0.02) and skewness (p = 0.008) between the levels. At the extracranial level we did not find any significant differences in the mean arterial flow, pulse flow or skewness between aHT+ and aHT-. There was a significant difference in kurtosis at the extracranial level between the aHT+ and aHT- (p = 0.03). At the intracranial level, there were no significant differences in all parameters. Conclusion: Results showed a difference between cerebral vasculature in AD for aHT+ and aHT- groups. This is probably related to the loss of arterial compliance induced by the degradation of the vascular system.

Introdução: Estudos demonstram a potencial deterioração da vascularização cerebral e a provável relação da hipertensão na doença de Alzheimer (DA). Objetivo: O objetivo foi avaliar o potencial impacto da hipertensão no fluxo vascular cerebral numa amostra de pacientes de Alzheimer. Métodos: foram selecionados 19 pacientes com DA, incluindo 10 com hipertensão (aHT+) e 9 sem hipertensão (aHT+). Foram submetidos a avaliação clínica e a um protocolo de ressonância magnética de contraste de fase para avaliação de fluxo. A distribuição de fluxo arterial cerebral foi avaliada através dos índices de curtose e assimetria nos níveis intra e extracraniano. Resultados: Não foram encontradas diferenças significativas no fluxo arterial médio, no fluxo de pulso e curtose entre os níveis da população DA aHT+. Houve uma diference significativa na assimetria entre os níveis extra e intracranianos (p = 0,01). Não foram encontradas diferenças significativas no fluxo arterial médio entre os níveis da população DA aHT-. Uma diferença significativa foi observada no fluxo de pulso (p = 0,03), na curtose (p = 0,02) e na assimetria (p = 0,008) entre os níveis. Não foram observadas diferenças significativas no fluxo arterial médio, no fluxo de pulso ou na assimetria entre aHT+ e aHT- para o nível extracraniano. Foi observada diferença significativa na curtose extracraniana entre aHT+ e AHT- (p = 0,03). Não houve diferença significativa em todos os parâmetros do nível intracraniano. Conclusão: Os resultados mostraram uma diferença entre a vasculatura cerebral nos grupos de DA aHT+ e aHT-. Isso está provavelmente relacionado à perda de complacência arterial induzida pela degradação do sistema vascular.

The role of PC-MRI in neurodegenerative diseases / O papel da RM com contraste nas doenças neurodegenerativas

Introduction: Neurodegenerative diseases, a major public health problem, could have a vascular origin. Phase-contrast magnetic resonance imaging (PC-MRI) enables reliable, non-invasive, and rapid measurements of cerebrospinal fluid (CSF) and blood flows, and evaluation of the mechanical coupling between cerebral blood and CSF flows throughout the cardiac cycle (CC). Objectives: Our purpose was to evaluate the potential of PC-MRI to the study of cerebral blood and CSF flows in patients with neurodegenerative diseases such as Alzheimer's disease (AD), Mild cognitive impairment with amnesic disorders (MCIa) and Vascular Dementia (VD). Methods: The elderly population consisted of 20 AD (age: 80 ± 5 years); 12 AD patients with vascular cerebral lesions (ADvasc) (age: 81 ± 5 years), 10 MCIa patients (age: 80 ± 7 years), and 8 VD patients (age: 78 ± 7 years) were identified. They underwent the same PC-MRI protocol and were compared to 13 age-matched Healthy Elderly (HE) (age: 71± 9 years). Arterial blood pressure was analyzed to detect patients with hypertension. Results: Significantly higher cerebral blood and CSF flows were observed in HE when compared to VD, AD and ADvasc, (p<0.05), but not MCIa patients who yielded the highest cerebral arterial and venous blood flows and stroke volumes compared to the other patients, (p<0.05). The highest oscillations of CSF were also detected in MCIa patients (p<0.05). Conclusion: Our preliminary data suggests an increase in cerebral arterial blood and CSF flows in MCIa. PC-MRI provides a new hydrodynamic view, which may help evaluate a potential role of cardiovascular alterations in neurodegenerative diseases.

Introdução: As doenças neurodegenerativas, um grande problema de saúde pública, podem ser de origem vascular. A ressonância magnética (RM) com contraste de fase permite medições confiáveis, não invasivas e rápidas do líquido cefalorraquidiano (LCR) e dos fluxos sanguíneos para avaliação do acoplamento mecânico de circulação cerebral e fluxo de LCR ao longo do ciclo cardíaco (CC). Objetivos: Nosso objetivo foi avaliar o potencial da RM com contraste de fase para o estudo do fluxo sanguíneo no cérebro e LCR em pacientes com doenças neurodegenerativas, como doença de Alzheimer (DA), comprometimento cognitivo leve (CCL) com distúrbios amnésicos e demência vascular (DV). Métodos: A população foi composta por 20 sujeitos idosos com DA (idade: 80 ± 5 anos); foram identificados 12 pacientes com lesões cerebrais vasculares (idade: 81 ± 5 anos), 10 pacientes com CCL e distúrbios amnésicos (idade: 80 ± 7 anos) e 8 com DV (idade: 78 ± 7 anos). Eles foram submetidos ao mesmo protocolo de RM com contraste de fase e comparados a 13 idosos saudáveis (idade: 71 ± 9 anos). A pressão arterial foi aferida para detectar pacientes com hipertensão arterial. Resultados: Observaram-se fluxos sanguíneos cerebrais e CSF significativamente maiores em pacientes com DV, DA e com lesões cerebrais (p<0,05), mas não nos pacientes com CCL, que tiveram os maiores fluxos arteriais e venosos cerebrais em relação aos demais pacientes (p<0,05). Maiores oscilações de LCR também foram detectadas em pacientes com CCL (p<0,05). Conclusão: Nossos dados preliminares sugerem um aumento no fluxo arterial cerebral e nos fluxos de LCR na CCL. A RM com contraste e fase fornece uma nova visão hidrodinâmica, o que pode ajudar a avaliar o possível papel das alterações cardiovasculares em doenças neurodegenerativas.