2010 12 24 Journal Club Functional MRI

Bruno Mascarenhas JMA NS I :

Bruno Mascarenhas JMA NS I Functional magnetic resonance imaging of the brain: A quick review Institute of Neurology Journal Club 24 th Dec 2010

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Vaghela V, Kesavadas C, Thomas B. Functional magnetic resonance imaging of the brain: A quick review. Neurol India [serial online] 2010 [cited 2010 Dec 22];58:879-85. Available from: http://www.neurologyindia.com/text.asp?2010/58/6/879/73735

functional magnetic resonance imaging (fMRI)  :

functional magnetic resonance imaging (fMRI) Non-invasive Map Hemodynamic changes Occurring focally in areas of brain involved in various functions motor sensory cognitive

Functional magnetic resonance imaging (fMRI) :

Functional magnetic resonance imaging (fMRI) A method which detects physiological changes occurring in the brain in response to any given task by using blood-oxygen-level-dependent (BOLD) changes. Major application localize eloquent regions of brain and their relation with surgically removable lesions.

other methods:

other methods Wada test direct cortical stimulation

unique advantages of fMRI:

unique advantages of fMRI non-invasiveness repeatability lack of radiation

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May not be a standalone investigation But has tremendous scope for being so in the near future Complementary to other more invasive methods in many areas of neuroscience research.

BOLD MR phenomenon:

BOLD MR phenomenon First observed by Ogawa and colleagues Change in blood oxygenation has a measurable effect with MR signal and can be used to monitor brain activation.

Basic Principles :

Basic Principles Generation of signal in fMRI is due to local reduction of deoxy-Hb as a result of neurovascular coupling and later uncoupling, know as the BOLD (blood-oxygen-level-dependent) effect.

Basic Principles :

Basic Principles During any particular task (e.g. finger tapping), there is local increase in neuronal activity and consequent oxygen consumption (i.e. cerebral metabolic rate of oxygen, CMRO 2 ) which increases deoxyhemoglobin . These along with other metabolic changes in turn send local signal, which results in increased cerebral blood flow (CBF) and cerebral blood volume (CBV) due to vasodilatation . Actually, this increase in oxygen delivery (CBF) overcompensates the local O 2 need (CMRO 2 ) and results in an excess of oxygenated blood at the local site .

Basic Principles :

Basic Principles MRI can measure this physiological change as oxyhemoglobin is diamagnetic and deoxyhemoglobin is paramagnetic and it induces local field inhomogeneities.

Basic Principles :

Basic Principles It has been known since 1936 that magnetic state of hemoglobin (Hb) changes with its oxygenation state. Deoxyhemoglobin induces microscopic field gradients that make the field more inhomogeneous and results in signal decay.

Basic Principles :

Basic Principles Oxygenated blood makes the local magnetic environment more uniform. As the field is more uniform, the signal decays less rapidly in this region and results in small increase in local signal. This small percentage increase in signal is recorded on fMRI. What we are measuring in fMRI is not the neuronal activity but the hemodynamic response to such activity and hence the signal in fMRI is delayed by 1-2 s and reaches its peak at 5-10 s.

Technique :

Technique The basic requirement to get fMRI signal is to identify activated voxels while patient performs the task. For this purpose, fast imaging sequence like echo planar imaging (EPI) is used, which allows collection of data from entire brain within few seconds at the cost of low spatial resolution.

Technique :

Technique fMRI setup requires availability of audiovisual system and various tailor-made paradigms, which are used to guide the patient through the various stages of control and activity conditions. The experiment begins with explaining the patient regarding the task to earn patient co-operation which is vital for a proper result.

Technique :

Technique Within the scanner, various paradigms are presented to patient (e.g. finger movement for motor examination, tactile stimulus for somatosensory and visual/auditory commands for language examination). Images are obtained while patient performs the task, which is divided into control and active state.

Technique :

Technique This results in generation of large amount of data that are analyzed statistically to identify the area of brain activity corresponding to the task performed. This analysis could be done by real-time fMRI processing or by offline post-processing tools. Finally, data regarding the activated brain areas are superimposed on high-resolution images like 3D SPGR/ FLASH or 3D-FLAIR

fMRI Applications :

fMRI Applications Epilepsy Imaging Pre-operative Assessment of Brain Tumors Alzheimer's Disease Dyslexia Cerebral A-V Malformation Assessment of Brain Plasticity Neuropsychological Disorders Cognitive Impairment After Traumatic Brain Injury

Epilepsy Imaging :

Epilepsy Imaging Pre-surgical localization of eloquent cortex Pre-operative mapping of motor cortex Mapping of somatosensory cortex Language lateralization Mapping of memory system Spontaneous ictal activity localization

Pre-operative Assessment of Brain Tumors :

Pre-operative Assessment of Brain Tumors Pre-surgical localization of eloquent cortex Pre-operative mapping of motor cortex Mapping of somatosensory cortex Language lateralization Mapping of memory system

Alzheimer's Disease :

Alzheimer's Disease A decrease in activation of MTL has been found in the patients with mild AD as compared to healthy volunteers using visual memory encoding. Patient of AD or people with high risk of AD have shown larger area of activation on fMRI study during memory task as compared to normal adults, which may explain the compensatory mechanism of brain. In a recent prospective study, the author has shown that functional changes in the posteromedial cortices (precuneus and posterior cingulate gyrus) may be a better fMRI marker of memory impairment than those in the hippocampus. Thus fMRI could potentially be used to identify person with high risk for development of AD based on these observations. Recently many resting state fMRI studies have provided considerable insight into the understanding of this elusive disease.

 Dyslexia :

Dyslexia Considerable research is going on in this field. fMRI has provided answers in many areas of dyslexia research, resulting in better understanding of this condition. These applications can be divided as (1) identification of abnormal circuit in dyslexic patients: Pattern of activation on fMRI is different between normal and dyslexic individuals with latter showing dysfunction in posterior reading circuit (e.g. superior temporal gyrus, temporo-parietal gyrus and angular gyrus); (2) assessment of compensatory mechanisms in a dyslexic person: increased activation of left and right inferior frontal gyrus has been found in dyslexic readers than in normal controls and (3) effect of training: with reading interventions change in brain activation of dyslexic reader has been found, which is similar to normal reader in the form of activation of left occipito-temporal area.

Cerebral A-V Malformation :

Cerebral A-V Malformation The fMRI can be challenging in patients with AVM due to flow abnormality interfering with BOLD signal. Many studies have assessed the reliability and technical feasibility of pre-op fMRI in AVM patients. It may give information such as possible postop deficit, eloquent areas to be avoided by the neurosurgeon and reorganization of functional area to same or opposite hemisphere. Correlation has been found between postop patient recovery/deficit and extent of reappearance/disappearance of functional activity on fMRI.

Assessment of Brain Plasticity :

Assessment of Brain Plasticity Brain has an important property of plasticity, which aims at maintaining optimal brain function through reorganization of brain areas from damaged or functionally sub-optimal areas to normal areas. Motor reorganization in patients with stroke and brain tumors has been shown by many researchers. Study of brain plasticity in case of AVM has shown evidence of interhemispheric transfer of language function (verbal fluency related to left frontal lobe) to right frontal lobe. However, it may still be unclear whether these activations are a compensatory mechanism or just a reorganization of existing alternate mechanisms.

 Neuropsychological Disorders :

Neuropsychological Disorders Prefrontal cortex, anterior cingulate cortex (ACC), insula and striatal structures are the major areas for the regulation and modulation of mood in human beings. Increase in ventral striatal and dorsal ACC activity and decrease in prefrontal cortical activity has been shown in manic patients. In patients with post-traumatic stress disorder while viewing of emotional facial expressions, there is evidence for increased amygdala activity and diminished medial prefrontal cortex responsively.

Cognitive Impairment After Traumatic Brain Injury :

Cognitive Impairment After Traumatic Brain Injury fMRI has been used to assess impairment of cognition in patient after trauma. In one study during a working memory task, pattern of activation in frontal, temporal and parietal region was similar in patients and controls with more dispersed and right lateralized activation in the former. Another author has shown relative decrease in ACC activity in traumatic brain injury patient as compared to controls probably secondary to destruction of neural networks after diffuse axonal injury.

Advances in fMRI :

Advances in fMRI Brain-computer interface: Brain-computer interface allows controlling the computer hardware through individual thoughts. Potential applications of this method can be in rehabilitation of physically handicapped people and in study of behavioral effects. Intraoperative fMRI: Use of neuronavigation in combination with fMRI to assist the accuracy and safety of the surgeon is now the reality. Wurm et al. has shown use of computer-assisted fMRI integration to plan complex surgery and to decide surgical extent.

Limitations of fMRI :

Limitations of fMRI Bold signal represent hemodynamic response to neuronal activity and hence it is an indirect measure of neuronal activity and not a direct effect. BOLD signal is highly sensitive to subject motion and so patient cooperation is mandatory and fMRI on non-cooperative or mentally subnormal patients becomes a challenge. Proper explanation about the procedure and practice sessions before the actual experiment is essential for a good study. Universal protocols for performing fMRI are yet to be standardized and most of the institutions are using tailor-made protocols.

Limitations of fMRI :

Limitations of fMRI BOLD signal is very weak and falls in the range of scanner noise and hence many statistical methods are used to ensure proper smoothing and co-registration of images, which may themselves introduce further errors. Although many authors have studied the validity of fMRI in comparison to conventional methods (e.g. Wada test), large-scale prospective studies are needed to support these findings. Many factors alter the BOLD response such as drug, age, attention or brain pathology, hence the interpretation become difficult in presence of such confounding factors

Conclusion :

Conclusion In the past two decades fMRI has stretched its horizon from being a mere research tool to a highly relevant clinical investigation for surgical planning, be it in epilepsy surgery or brain neoplasms. Its role in dyslexia, Alzheimer disease, brain AVM, psychological disorder and assessment of brain plasticity has been recognized and increasing number of new applications are emerging every day.

Wada test:

Wada test The Wada test, named after Canadian neurologist Juhn Atsushi Wada (of the University of British Columbia), also known as the "intracarotid sodium amobarbital procedure" (ISAP), is used to establish which cerebral functions are localized to which hemisphere.

Wada Test - History:

Wada Test - History He developed the test while a medical resident in Japan just after World War II, when he was receiving training in neurosurgery. Recognizing that there was no available test for cerebral dominance for speech, Wada developed the carotid amytal test. He published the initial description in 1949, in Japanese. During later training at the Montreal Neurological Institute, he introduced the test to the English-speaking world.

Wada Test - History:

Wada Test - History conducted with the patient awake. Essentially, a barbiturate (which is usually sodium amobarbital) is introduced into one of the internal carotid arteries via a cannula or intra-arterial catheter from the femoral artery. The drug is injected into one hemisphere at a time. The effect is to shut down any language and/or memory function in that hemisphere in order to evaluate the other hemisphere ("half of the brain").

Wada Test - History:

Wada Test - History Then the patient is engaged in a series of language and memory related tests. The memory is evaluated by showing a series of items or pictures to the patient so that within a few minutes as soon as the effect of the medication is dissipated, the ability to recall can be tested. There is currently great variability in the processes used to administer the test, and so it is difficult to compare results from one patient to the other

Wada Test - History:

Wada Test - History The test is usually performed prior to ablative surgery for epilepsy and sometimes prior to tumor resection. The aim is to determine which side of the brain is responsible for certain vital cognitive functions, namely speech and memory. The risk of damaging such structures during surgery can then be assessed, and the need for awake craniotomies can be determined as well.

Wada Test - History:

Wada Test - History The Wada test has several interesting side-effects. Drastic personality changes are rarely noted, but disinhibition is common. Also, contralateral hemiplegia, hemineglect and shivering are often seen. During one injection, typically the left hemisphere, the patient will have impaired speech or be completely unable to express or understand language.

Wada Test - History:

Wada Test - History Although the patient may not be able to talk, sometimes their ability to sing is preserved. This is because music and singing utilizes a different part of the brain than speech and language. Recovery from the anesthesia is rapid, and EEG recordings and distal grip strength are used to determine when the medication has worn off.

Wada Test - History:

Wada Test - History Generally, recovery of speech is dysphasic (contains errors in speech or comprehension) after a dominant hemisphere injection. Although generally considered a safe procedure, there are at least minimal risks associated with the angiography procedure used to guide the catheter to the internal carotid artery. As such, efforts to utilize non-invasive means to determine language and memory laterality (e.g. fMRI, magnetoencephalography and near-infrared spectroscopy) are being researched.

Electrocorticography:

Electrocorticography Electrocorticography (ECoG) is the practice of using electrodes placed directly on the exposed surface of the brain to record electrical activity from the cerebral cortex. ECoG may be performed either in the operating room during surgery (intraoperative ECoG) or outside of surgery (extraoperative ECoG). Because a craniotomy (a surgical incision into the skull) is required to implant the electrode grid, ECoG is an invasive procedure. ECoG is currently considered to be the “gold standard” for defining epileptogenic zones in clinical practice.

Electrocorticography:

Electrocorticography The ECoG recording is performed from electrodes placed on the exposed cortex. Craniotomy may be performed either under general anesthesia or under local anesthesia if patient interaction is required for functional cortical mapping. Electrodes are then surgically implanted on the surface of the cortex, with placement guided by the results of preoperative EEG and magnetic resonance imaging (MRI). Electrodes may either be placed outside the dura mater (epidural) or under the dura mater (subdural).

Electrocorticography:

Electrocorticography ECoG electrode arrays typically consist of sixteen sterile, disposable stainless steel, carbon tip, platinum, or gold ball electrodes, each mounted on a ball and socket joint for ease in positioning. These electrodes are attached to an overlying frame in a “crown” or “halo” configuration. Subdural strip and grid electrodes are also widely used in various dimensions, having anywhere from 4 to 64 electrode contacts. The grids are transparent, flexible, and numbered at each electrode contact.

Electrocorticography:

Electrocorticography Standard spacing between grid electrodes is 1 cm; individual electrodes are typically 5 mm in diameter. The electrodes sit lightly on the cortical surface, and are designed with enough flexibility to ensure that normal movements of the brain do not cause injury. A key advantage of strip and grid electrode arrays is that they may be slid underneath the dura mater into cortical regions not exposed by the craniotomy. Strip electrodes and crown arrays may be used in any combination desired. Depth electrodes may also be used to record activity from deeper structures such as the hippocampus.

Direct cortical electrical stimulation (DCES):

Direct cortical electrical stimulation (DCES) Direct cortical electrical stimulation (DCES) is frequently performed in concurrence with ECoG recording for functional mapping of the cortex and identification of critical cortical structures. When using a crown configuration, a handheld wand bipolar stimulator may be used at any location along the electrode array. However, when using a subdural strip, stimulation must be applied between pairs of adjacent electrodes due to the nonconductive material connecting the electrodes on the grid. Electrical stimulating currents applied to the cortex are relatively low, between 2 to 4 mA for somatosensory stimulation, and near 15 mA for cognitive stimulation.

Direct cortical electrical stimulation (DCES):

Direct cortical electrical stimulation (DCES) The functions most commonly mapped through DCES are primary motor, primary sensory, and language. The patient must be alert and interactive for mapping procedures, though patient involvement varies with each mapping procedure. Language mapping may involve naming, reading aloud, repetition, and oral comprehension; somatosensory mapping requires that the patient describe sensations experienced across the face and extremities as the surgeon stimulates different cortical regions

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Thank You