6 Functional Neuroimaging II

10.1055/b-0039-171725

6 Functional Neuroimaging II

Walid I. Essayed, Prashin Unadkat and Alexandra J. Golby

Abstract

Functional neuroimaging is a constantly evolving and increasingly important tool for modern neurosurgery including preoperative and intraoperative surgical guidance. With the development of these modern techniques, frontiers between anatomical, microstructural, metabolic, and functional imaging have become blurred. In this chapter, we review the state of the art of currently available methods, while emphasizing advantages and limitations of each technique, The chapter is structured around the physiological basis of the modalities: metabolic for fMRI, PET and indirectly tractography, versus electrophysiological for TMS and MSI.

Functional neuroimaging is a continuously evolving and increasingly important tool for modern neurosurgery including preoperative and intraoperative surgical guidance. In this chapter, we will review the state of the art of currently available methods, while emphasizing advantages and limitations of each technique, understanding of which is imperative for judicious use and interpretation.

With the development of these modern techniques, frontiers between anatomical, microstructural, metabolic, and functional imaging have become blurred. Techniques such as fMRI (functional Magnetic Resonance Imaging) and PET (Positron Emission Tomography) are directly based on metabolic underpinnings of the biological function, while tractography is based on the structural substrate of the function, specifically water molecule distribution along myelinated white matter fibers axons. Other modalities such as TMS (Transcranial Magnetic Stimulation) and MSI (Magnetic Source Imaging) are founded on the electromagnetic properties associated with the electrical neuronal function. We limit our review to these techniques and will not include other methods such as perfusion-MR, MR spectroscopy, and EEG. The chapter is structured around specific imaged function: metabolic for fMRI, PET, and indirectly tractography, versus electrophysiological for TMS and MSI.

Metabolic Function Functional Magnetic Resonance Imaging is the most popular modality used to understand the functional neuroanatomy of the the cortex, and is clinically used to understand the relationship of functional areas with respect to some lesion or underlying pathology. The growing popularity of clinical fMRI is in part due to the increasing availability of high field strength magnets at most centers, relatively short scan time, non-invasiveness, and the absence of any known side effects.

Direct Methods The physiological basis of fMRI is the blood oxygen level dependent (BOLD) signal. Principally based on the phenomenon of neurovascular coupling, task related neuronal activity within specific areas of the cortex leads to a greater increase in cerebral blood flow (CBF) as compared to the increased cerebral metabolic rate of oxygen (CMRO₂) within that region.

fMRI Specifically, deoxyhemoglobin is used as an endogenous paramagnetic contrast agent, leading to a drop in the fMRI signal. In the region of neuronal activation, dilution of paramagnetic substance by a relative increase in oxyhemoglobin, which is diamagnetic, leads to an overall increase in the fMRI signal on the T2*-weighted images, which forms the basis of BOLD fMRI. Gradient-echo fMRI is the most widely used sequence for clinical applications due to its high sensitivity. High resolution fMRI is heavily dependent on a favorable signal to noise ratio.

6.1 Artifacts and Limitations

Several imaging artifacts can adversely impact the quality of fMRI. Motion related artifacts, caused by voluntary movement or breathing can compromise results. Susceptibility artifacts from prior surgeries or tissue interfaces can lead to signal drop-out. BOLD signal from large venous structures may give false-positive results and do not represent true neuronal activity. The neurovascular decoupling that occurs due to abnormal hemodynamic autoregulation around tumors, can lead to false negative results. Lastly, although fMRI has excellent spatial resolution, the delayed hemodynamic response to neuronal activity reduces the temporal resolution compared to electrophysiologic brain mapping techniques like Magnetoencephalography (MEG).

6.2 Task Paradigm Selection

Since its advent, fMRI has been increasingly useful to guide medical and surgical care in different brain pathologies. While multiple functions have been mapped, commonly tested in presurgical evaluations are motor, sensory, language, vision and occasionally memory.

Depending on the function of interest, the patient performs a specific task paradigm with a “block” or “event-related” design. Patient preparation with pre-exam explanation and assessment of the ability to follow task instructions reduces false-positive and false-negative results. Careful adjustment of task paradigms depending on patient age or pre-existing neurological deficit may be warranted to insure adequate task performance.

6.3 Key Applications

Motor, sensory, and language mapping for risk stratification and surgical planning in tumor resection and epilepsy surgery (▶ Fig. 6.1). ¹ ^, ²
Validation and guidance of other techniques: preoperative white matter tractography, intraoperative direct cortical stimulation guidance, decreasing the risk of induced seizures and patient fatigue during awake surgery (▶ Fig. 6.1). ²
Assessment of neuroplasticity and its prognostic correspondences. ³

**Fig. 6.1** 30 y.o. female with a left W.H.O grade III oligodendroglioma in the motor cortex. The lesion has a relatively homogenous hypo T1 and hyper T2 signal, without any contrast enhancement. The PET study (F-18 fluroethyltyrosine) shows areas of high uptake within the lesion. These results directed the focused histopathological assessment, confirming the anaplastic nature of this lesion.

6.4 PET

Positron Emission Tomography (PET) is the tomographic acquisition of annihilation photons released by positron emitting radiotracers, which is frequently integrated with computed x-ray tomography (CT) providing the basis for structural imaging. Cellular uptake of the positron emitting tracers can be highly variable but is usually measurable in hours, leading to low temporal resolution. This represented the major limitation for the use of PET as a method of normal brain functional imaging. Recently promising amino acid uptake-based radiotracers have been developed, particularly for brain imaging. These radiotracer advances associated with development of acquisition methods are progressively opening major diagnostic, therapeutic, and prognostic applications for the use of PET in brain tumor management.