5-ALA induced PpIX fluorescence spectroscopy in neurosurgery: a review.

The review begins with an overview of the fundamental principles/physics underlying light, fluorescence, and other light-matter interactions in biological tissues. It then focuses on 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence spectroscopy methods used in neurosurgery (e.g., intensity, time-resolved) and in so doing, describe their specific features (e.g., hardware requirements, main processing methods) as well as their strengths and limitations. Finally, we review current clinical applications and future directions of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence spectroscopy in neurosurgery.

An Explicit Estimated Baseline Model for Robust Estimation of Fluorophores Using Multiple-Wavelength Excitation Fluorescence Spectroscopy.

Spectroscopy is a popular technique for identifying and quantifying fluorophores in fluorescent materials. However, quantifying the fluorophore of interest can be challenging when the material also contains other fluorophores (baseline), particularly if the emission spectrum of the baseline is not well-defined and overlaps with that of the fluorophore of interest. In this work, we propose a method that is free from any prior assumptions about the baseline by utilizing fluorescence signals at multiple excitation wavelengths. Despite the nonlinearity of the model, a closed-form expression of the least squares estimator is also derived. To evaluate our method, we consider the practical case of estimating the contributions of two forms of protoporphyrin IX (PpIX) in a fluorescence signal. This fluorophore of interest is commonly utilized in neuro-oncology operating rooms to distinguish the boundary between healthy and tumor tissue in a type of brain tumor known as glioma. Using a digital phantom calibrated with clinical and experimental data, we demonstrate that our method is more robust than current state-of-the-art methods for classifying pathological status, particularly when applied to images of simulated clinical gliomas. To account for the high variability in the baseline, we are examining various scenarios and their corresponding outcomes. In particular, it maintains the ability to distinguish between healthy and tumor tissue with an accuracy of up to 87%, while the ability of existing methods drops near 0%.

Spectral complexity of 5-ALA induced PpIX fluorescence in guided surgery: a clinical study towards the discrimination of healthy tissue and margin boundaries in high and low grade gliomas.

Gliomas are diffuse and hard to cure brain tumors. A major reason for their aggressive behavior is their property to infiltrate the brain. The gross appearance of the infiltrative component is comparable to normal brain, constituting an obstacle to extended surgical resection. 5-ALA induced PpIX fluorescence measurements enable gains in sensitivity to detect infiltrated cells, but still lack sensitivity to get accurate discrimination between the tumor margin and healthy tissue. In this fluorescence spectroscopic study, we assume that two states of PpIX contribute to total fluorescence to get better discrimination of healthy tissues against tumor margins. We reveal that fluorescence in low-density margins of high-grade gliomas or in low-grade gliomas is mainly influenced by the second state of PpIX centered at 620 nm. We thus conclude that consideration of the contributions of both states to total fluorescence can help to improve fluorescence-guided resection of gliomas by discriminating healthy tissues from tumor margins.

Measuring brain hemodynamic changes in a songbird: responses to hypercapnia measured with functional MRI and near-infrared spectroscopy.

Songbirds have been evolved into models of choice for the study of the cerebral underpinnings of vocal communication. Nevertheless, there is still a need for in vivo methods allowing the real-time monitoring of brain activity. Functional Magnetic Resonance Imaging (fMRI) has been applied in anesthetized intact songbirds. It relies on blood oxygen level-dependent (BOLD) contrast revealing hemodynamic changes. Non-invasive near-infrared spectroscopy (NIRS) is based on the weak absorption of near-infrared light by biological tissues. Time-resolved femtosecond white laser NIRS is a new probing method using real-time spectral measurements which give access to the local variation of absorbing chromophores such as hemoglobins. In this study, we test the efficiency of our time-resolved NIRS device in monitoring physiological hemodynamic brain responses in a songbird, the zebra finch (Taeniopygia guttata), using a hypercapnia event (7% inhaled CO(2)). The results are compared to those obtained using BOLD fMRI. The NIRS measurements clearly demonstrate that during hypercapnia the blood oxygen saturation level increases (increase in local concentration of oxyhemoglobin, decrease in deoxyhemoglobin concentration and total hemoglobin concentration). Our results provide the first correlation in songbirds of the variations in total hemoglobin and oxygen saturation level obtained from NIRS with local BOLD signal variations.