Feasibility of glioblastoma tissue response mapping with physiologic BOLD imaging using precise oxygen and carbon dioxide challenge

Abstract

Objectives: Innovative physiologic MRI development focuses on depiction of heterogenous vascular and metabolic features in glioblastoma. For this feasibility study, we employed blood oxygenation leveldependent (BOLD) MRI with standardized and precise carbon dioxide (CO2) and oxygen (O2) modulation to investigate specific tumor tissue response patterns in patients with newly diagnosed glioblastoma. Materials and methods: Seven newly diagnosed untreated patients with suspected glioblastoma were prospectively included to undergo a BOLD study with combined CO2 and O2 standardized protocol. %BOLD signal change/mmHg during hypercapnic, hypoxic, and hyperoxic stimulus was calculated in the whole brain, tumor lesion and segmented volumes of interest (VOI) [contrast-enhancing (CE) -tumor, necrosis and edema] to analyze their tissue response patterns. Results: Quantification of BOLD signal change after gas challenges can be used to identify specific responses to standardized stimuli in glioblastoma patients. Integration of this approach with automatic VOI segmentation grants improved characterization of tumor subzones and edema. Magnitude of BOLD signal change during the 3 stimuli can be visualized at voxel precision through color-coded maps overlayed onto whole brain and identified VOIs. Conclusions: Our preliminary investigation shows good feasibility of BOLD with standardized and precise CO2 and O2 modulation as an emerging physiologic imaging technique to detail specific glioblastoma characteristics. The unique tissue response patterns generated can be further investigated to better detail glioblastoma lesions and gauge treatment response.

Hemodynamic Imaging in Cerebral Diffuse Glioma—Part B: Molecular Correlates, Treatment Effect Monitoring, Prognosis, and Future Directions

“…Interestingly, oxygen modulation has been also recently proposed as a means to study cerebral perfusion through rapid transient hemoglobin desaturation with the potential to substitute contrast-based perfusion [ 202 , 203 , 204 ] with advantages also relating to the avoidance of gadolinium contrast use [ 205 ], but application in the study of brain tumors is still lacking. Independently of these developments, the possibility of precise end-tidal oxygen modulation in isocapnic conditions has been preliminarily investigated as a means to provide a novel “imaging biomarker” to detail glioblastoma lesion microvascular features during BOLD imaging, exploiting hypoxia and hyperoxia as BOLD contrasts [ 206 ].…”

Transient deoxyhemoglobin formation as a contrast for perfusion MRI studies in patients with brain tumors: a feasibility study

“…Moving away from resting perfusion assessment, other approaches may be employed to investigate intrinsic tissue features by dissecting specific BOLD signal changes characteristics during gas control. A preliminary study demonstrated the feasibility of such technique, with a small cohort of glioblastoma patients exhibiting unique tissue response patterns during hypoxic, hyperoxic and hypercapnic stimuli ( Stumpo et al, 2021 ). For this reason, a longitudinal cohort study after optimization of the hypoxic stimulus is currently ongoing.…”

“…During the echo-planar imaging (EPI) sequence acquisition, 160 volumes were acquired corresponding to a duration of circa 5 minutes. Acquisition parameters of T1-CE, FLAIR, T2 as per standard brain tumor protocol have been described in previously published article ( Stumpo et al, 2021 ). For a subgroup of patients, clinical-diagnostic work-up required execution of a gadolinium (Dotarem) enhanced DSC-MRI GRE-EPI, FOV 100 × 100 mm 2 , resolution 128 × 128, TR/TE 2040/36, FA 90°.…”

“…Previous literature has focused on BOLD-contrast for functional MRI and task-based pre-surgical mapping (as neural activation induces changes in regional blood flow) (Glover, 2011;Zacà et al, 2014), or resting-state fMRI for functional architecture inference (Lee et al, 2013;Stoecklein et al, 2020), as well as characterization of cerebrovascular reactivity during vasodilatory stimulus (Fierstra et al, 2013;Fierstra et al, 2016;Fierstra et al, 2018;Fisher et al, 2018;Muscas et al, 2020;Sebök et al, 2020;Sebök et al, 2021). Only recently has the possibility to induce a reproducible and standardized transient bolus of deoxygenated blood (while controlling for competing PCO 2 effects) -in combination with the high temporal resolution of EPI sequence -become focus of attention in the setting of perfusion quantification (Poublanc et al, 2021;Vu et al, 2021;Sayin et al, 2022;Sebök et al, 2023a).…”

Association between the Anatomical Location of Glioblastoma and Its Evaluation with Clinical Considerations: A Systematic Review and Meta-Analysis

“…The clinical implications associated with the anatomical location of glioblastoma were analyzed in different articles, with a total of 107 articles in which a relationship was not made between the region of glioblastoma and a clinical implication [10,11,13,[18][19][20][21][22][70][71][72][73][74][75][77][78][79][80][81][82][83][84][85][87][88][89][90][91][92][93][94][95][96][97][98][99][100]104,105,[107][108][109][110][111][112][113][114][115][116]…”