Brain Perfusion Imaging Under Acetazolamide Challenge for Detection of Impaired Cerebrovascular Reserve Capacity: Positive Findings with 15O-Water PET in Patients with Negative 99mTc-HMPAO SPECT Findings

Acker, Güliz; Lange, Catharina; Schatka, Imke; Pfeifer, Andreas; Czabanka, Marcus; Vajkoczy, Peter; Buchert, Ralph

doi:10.2967/jnumed.117.195818

Cited by 23 publications

(18 citation statements)

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“…Before indicating a surgical revascularization, identification of cerebral vascular territories with insufficient perfusion is crucial to ensure a successful tailored treatment for each patient. This, however cannot be achieved with routine MRI and digital subtraction angiography (DSA) alone, but hemodynamic modalities like H 2 15 O positron emission tomography (PET) or Single Photon Emission Computed Tomography (SPECT) with acetazolamide (ACZ) challenge, among others, remain indispensible (Pandey and Steinberg, 2011; Lee et al, 2009; Roder et al, 2018; Acker et al, 2018). Main disadvantages of H 2 15 O PET with ACZ challenge include high costs and limited availability.…”

Section: Introductionmentioning

confidence: 99%

Hypercapnic BOLD MRI compared to H215O PET/CT for the hemodynamic evaluation of patients with Moyamoya Disease

Hauser

Seeger

Bender

et al. 2019

NeuroImage: Clinical

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Background and purposePatients with Moyamoya Disease (MMD) need hemodynamic evaluation of vascular territories at risk of stroke. Today's investigative standards include H215O PET/CT with pharmacological challenges with acetazolamide (ACZ). Recent developments suggest that CO2-triggered blood‑oxygen-level-dependent (BOLD) functional MRI might provide comparable results to current standard methods for evaluation of territorial hemodynamics, while being a more widely available and easily implementable method. This study examines results of a newly developed quantifiable analysis algorithm for CO2-triggered BOLD MRI in Moyamoya patients and correlates the results with H215O PET/CT with ACZ challenge to assess comparability between both modalities.MethodsCO2-triggered BOLD MRI was performed and compared to H215O PET/CT with ACZ challenge in patients with angiographically proven MMD. Images of both modalities were analyzed retrospectively in a blinded, standardized fashion by visual inspection, as well as with a semi-quantitative analysis using stimuli-induced approximated regional perfusion-weighted data and BOLD-signal changes with reference to cerebellum.Results20 consecutive patients fulfilled the inclusion criteria, a total of 160 vascular territories were analyzed retrospectively. Visual analysis (4-step visual rating system) of standardized, color-coded cerebrovascular reserve/reactivity maps showed a very strong correlation (Spearman's rho = 0.9, P < 0.001) between both modalities. Likewise, comparison of approximated regional perfusion changes across vascular territories (normalized to cerebellar change) reveal a highly significant correlation between both methods (Pearson's r = 0.71, P < 0.001).ConclusionsThe present analysis indicates that CO2-triggered BOLD MRI is a very promising tool for the hemodynamic evaluation of MMD patients with results comparable to those seen in H215O PET/CT with ACZ challenge. It therefore holds future potential in becoming a routine examination in the pre- and postoperative evaluation of MMD patients after further prospective evaluation.

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Section: Introductionmentioning

confidence: 99%

Hypercapnic BOLD MRI compared to H215O PET/CT for the hemodynamic evaluation of patients with Moyamoya Disease

Hauser

Seeger

Bender

et al. 2019

NeuroImage: Clinical

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“…Improvement of the posttraumatic course of animals could be achieved by only a single dose of the substance. While ACZ has been widely used in neurosurgical practice (15–22, 80, 84, 85), translating our treatment regime into clinical practice is hampered by a couple of shortcomings that need to be addressed in follow-up studies. First, while the CHI was deliberately chosen to perform DC on the not previously trephined skull, and to demonstrate a well-delineated injury epicenter by MRI (31, 49), this model does not necessarily demonstrates all the features of severe head trauma as seen in clinical routine.…”

Section: Discussionmentioning

confidence: 99%

“…Some of these properties have been successfully integrated into clinical practice, to decrease intracranial pressure (ICP) via reduced CSF production in benign intracranial hypertension (15, 16). Also the ACZ-mediated vasodilation has been utilized for treatment of acute mountain disease (17) and for diagnostic neuroimaging (18–22). Furthermore, in traumatic brain injury (TBI) experiments, antiedematous, and neuroprotective effects of ACZ treatment could be demonstrated, and its therapeutic potential has been postulated (3, 6, 7).…”

Section: Introductionmentioning

confidence: 99%

Brain Edema Formation and Functional Outcome After Surgical Decompression in Murine Closed Head Injury Are Modulated by Acetazolamide Administration

et al. 2019

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Acetazolamide (ACZ), carbonic anhydrase inhibitor, has been successfully applied in several neurosurgical conditions for diagnostic or therapeutic purposes. Furthermore, neuroprotective and anti-edematous properties of ACZ have been postulated. However, its use in traumatic brain injury (TBI) is limited, since ACZ-caused vasodilatation according to the Monro-Kellie doctrine may lead to increased intracranial blood volume / raise of intracranial pressure. We hypothesized that these negative effects of ACZ will be reduced or prevented, if the drug is administered after already performed decompression. To test this hypothesis, we used a mouse model of closed head injury (CHI) and decompressive craniectomy (DC). Mice were assigned into following experimental groups: sham, DC, CHI, CHI+ACZ, CHI+DC, and CHI+DC+ACZ ( n = 8 each group). 1d and 3d post injury, the neurological function was assessed according to Neurological Severity Score (NSS) and Beam Balance Score (BBS). At the same time points, brain edema was quantified by MRI investigations. Functional impairment and edema volume were compared between groups and over time. Among the animals without skull decompression, the group additionally treated with acetazolamide demonstrated the most severe functional impairment. This pattern was reversed among the mice with decompressive craniectomy: CHI+DC treated but not CHI+DC+ACZ treated animals showed a significant neurological deficit. Accordingly, radiological assessment revealed most severe edema formation in the CHI+DC group while in CHI+DC+ACZ animals, volume of brain edema did not differ from DC-only animals. In our CHI model, the response to acetazolamide treatment varies between animals with decompressive craniectomy and those without surgical treatment. Opening the cranial vault potentially creates an opportunity for acetazolamide to exert its beneficial effects while vasodilatation-related risks are attenuated. Therefore, we recommend further exploration of this potentially beneficial drug in translational research projects.

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“…For patients with disease-affected territories and as yet normal perfusion and reserves (not hemodynamically affected patients), strict and regular follow-ups are recommended [1,3,4]. Such hemodynamic evaluation can be performed by H 2 15 O PET with acetazolamide (ACZ) challenge, among others [5][6][7][8]. This however has disadvantages such as limited availability, need of ACZ injection, high costs, and radiation exposure [9].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Reproducibility of CO2-Triggered BOLD MRI for the Hemodynamic Evaluation of Adult Patients with Moyamoya Angiopathy

et al. 2021

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Background and Purpose: Hemodynamic evaluation of moyamoya patients is crucial to decide the treatment strategy. Recently, CO2-triggered BOLD MRI has been shown to be a promising tool for the hemodynamic evaluation of moyamoya patients. However, the longitudinal reliability of this technique in follow-up examinations is unknown. This study aims to analyze longitudinal follow-up data of CO2-triggered BOLD MRI to prove the reliability of this technique for long-term control examinations in moyamoya patients. Methods: Longitudinal CO2 BOLD MRI follow-up examinations of moyamoya patients with and without surgical revascularization have been analyzed for all 6 vascular territories retrospectively. If revascularization was performed, any directly (by the disease or the bypass) or indirectly (due to change of collateral flow after revascularization) affected territory was excluded based on angiography findings (group 1). In patients without surgical revascularization between the MRI examinations, all territories were analyzed (group 2). Results: Eighteen moyamoya patients with 39 CO2 BOLD MRI examinations fulfilled the inclusion criteria. The median follow-up between the 2 examinations was 12 months (range 4–29 months). For 106 vascular territories analyzed in group 1, the intraclass correlation coefficient was 0.784, p < 0.001, and for group 2 (84 territories), it was 0.899, p < 0.001. Within the total follow-up duration of 140 patient months, none of the patients experienced a new stroke. Conclusions: CO2 BOLD MRI is a promising tool for mid- and long-term follow-up examinations of cerebral hemodynamics in moyamoya patients. Systematic prospective evaluation is required prior to making it a routine examination.

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Brain Perfusion Imaging Under Acetazolamide Challenge for Detection of Impaired Cerebrovascular Reserve Capacity: Positive Findings with ¹⁵O-Water PET in Patients with Negative ^99mTc-HMPAO SPECT Findings

Cited by 23 publications

References 10 publications

Hypercapnic BOLD MRI compared to H215O PET/CT for the hemodynamic evaluation of patients with Moyamoya Disease

Hypercapnic BOLD MRI compared to H215O PET/CT for the hemodynamic evaluation of patients with Moyamoya Disease

Brain Edema Formation and Functional Outcome After Surgical Decompression in Murine Closed Head Injury Are Modulated by Acetazolamide Administration

Longitudinal Reproducibility of CO<sub>2</sub>-Triggered BOLD MRI for the Hemodynamic Evaluation of Adult Patients with Moyamoya Angiopathy

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