Estimation of Brain Deformation for Volumetric Image Updating in Protoporphyrin IX Fluorescence-Guided Resection

Abstract

Introduction: Fluorescence-guided resection (FGR) of brain tumors is an intuitive, practical and emerging technology for visually delineating neoplastic tissue exposed intraoperatively. Image guidance is the standard technique for producing 3-dimensional spatially coregistered information for surgical decision making. Both technologies together are synergistic: the former detects surface fluorescence as a biomarker of the current surgical margin while the latter shows coregistered volumetric neuroanatomy but can be degraded by intraoperative brain shift. We present the implementation of deformation modeling for brain shift compensation in protoporphyrin IX FGR, integrating these two sources of information for maximum surgical benefit. Methods: Two patients underwent FGR coregistered with conventional image guidance. Histopathological analysis, intraoperative fluorescence and image space coordinates were recorded for biopsy specimens acquired during surgery. A biomechanical brain deformation model driven by intraoperative ultrasound data was used to generate updated MR images. Results: Combined use of fluorescence signatures and updated MR image information showed substantially improved accuracy compared to fluorescence or the original (i.e., nonupdated) MR images, detecting only true positives and true negatives, and no instances of false positives or false negatives. Conclusion: Implementation of brain deformation modeling in FGR shows promise for increasing the accuracy of neurosurgical guidance in the delineation and resection of brain tumors.

Aminolevulinic acid (ALA)–protoporphyrin IX fluorescence guided tumour resection. Part 1: Clinical, radiological and pathological studies

“…45 In a novel application, Valdes et al applied PpIX positive coordinates recorded intraoperatively to refine the accuracy of a brain deformation model, in order to compensate MRI for intraoperative brain shift. 46 Applying the more sensitive fluorescence detection method of intraoperative spectrometry may considerably refine the accuracy of identifying tumour infiltration.…”

Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy

“…The introduction of the aminolevulinic acid (ALA)-protoporphyrin IX (PpIX) system has found great success clinically in fluorescence guided resection (FGR) for minimizing the amount of malignant glioma tissue remaining in the patient post-surgical resection in Germany, [1][2][3][4][5][6] and is ongoing in clinical trials in the United States [7][8][9][10] and Switzerland. 11 Current standard of care for brain cancer patients undergoing surgery includes magnetic resonance (MR) imaging prior to surgery to map tumor extent, surgical resection, and post-surgical MR imaging to determine if any contrast-enhancing tumor region remains.…”

“…However, tumor margins determined from conventional MR imaging [gadolinium (Gd) enhanced T1-weighted] and PpIX fluorescence often do not agree, 1 even with advanced algorithms to account for brain deformation during the surgical intervention. 8 This paper evaluates the correlation between tissue contrast from PpIX fluorescence and Gd-enhanced T1-weighted, absolute T2, and diffusion MR images using a highly infiltrative human glioma in a murine model. The ALA-PpIX system provides tumor to normal tissue contrast through production of PpIX in malignant tissues following ALA administration by overwhelming the heme biosynthesis pathway, found in all mammalian cells.…”

“…Diffusely growing tumors did not have as high, if any, image contrast in Gd enhanced MR images. A recent pilot study in two human cases 8 comparing pre-operative MRI to intrasurgical FGR fluorescence using a method to spatially register them, showed that there was synergy in using both methods to identify the diseased regions for resection, as assessed by sensitivity and specificity of detection.…”

ALA-induced PpIX fluorescence in epileptogenic tissue

“…PpIX is a fluorescent compound with a major excitation peak at ~ 400 nm, a major emission peak at ~635 nm, and a long emission shoulder extending to ~730 nm. ALA-induced PpIX fluorescence is emerging as a valuable intraoperative adjunct for resection of glioblastoma multiforme, as well as other tumor types that feature hypermetabolic activity [8][9][10][11] . Current applications of ALAinduced PpIX for FI involve exogenous administration of ALA which leads to selective accumulation of PpIX in neoplastic tissue.…”