fMRI and Brain Tumours
Certainly, fMRI takes pride of place in the presurgical evaluation of brain tumours. As stated in the introduction, fMRI is of inestimable value in locating eloquent areas when normal relationships between anatomy and function are lost (e.g. when a mass effect distorts the anatomical landmarks or when functional areas maybe relocated to other areas in the brain). However, in some situations, fMRI activation in and around tumours must be interpreted with caution.
Schreiber et al.  found that fMRI activation is reduced near glial tumours, but is usually not affected by non-glial tumours. They suggested that this phenomenon might be explained by the fact that glial tumours grow in a more infiltrative manner and thus alter the cellular architecture, whereas non-glial tumours show more delineation from normal tissue, leaving the cellular architecture intact.
Primary brain tumours, especially low-grade tumours, have been shown to have functional tissue preserved within the lesion itself. Negative findings may represent language cortex working, but having an activity level below the sensitivity of the technique and thus not being detected. Moreover, it is known, from both angiographic and MR studies, that tumour vasculature in malignant gliomas loses the ability to autoregulate. If the brain's ability to autoregulate the flow of blood is lost in brain tissue, which is still functioning, then this area may not respond to increased neural activity by a corresponding increase in blood flow . Another reason adduced by the same authors is the mass effect. Venous structures are normally under low pressure and are easily compressible. The increased tumour mass effect compresses the venules and larger veins, thereby speeding the egress of deoxyhaemoglobin-laden blood from the area of activation. This leads to a decrease in the relative concentration of deoxyhaemoglobin in the area of activation, which in turn results in an effective decrease in the difference in concentration of deoxyhae-moglobin between the resting and active states. This would lead to a decreased ability of fMR imaging to detect changes between the resting and active states .
However, intraoperative cortical mapping confirmed most of the fMRI findings and showed that the possible limitations of technique concerned only some selected cases and did not impede the successful identification of the eloquent cortex in the vast majority of patients of this kind.
fMRI and Epilepsy
Another important field of fMRI application is the presurgical evaluation of patients with refractory epilepsy. It is well known that about 90 % of well-selected patients become seizure-free after surgical treatment . As far as the surgical outcome is concerned, fMRI becomes an important tool for selecting and better characterizing these patients.
fMRI in fact plays a significant role not only in defining the lateralization of language functions, but also in localizing the specific language areas. As to this last point, it has been shown that patients with epilepsy tend to have more „bilateral" activation: they reveal a significantly higher recruitment of contralateral homologous language areas, compared to the normal controls. Moreover, the earlier the onset of dominant temporal lobe seizure foci, the more widespread and atypical the distribution of language areas; expressive and receptive language skills can also dissociate in people with brain lesions occurring early in life . In this context, fMRI becomes an invaluable help in mapping clinically relevant language functions in the epilepsy surgery population.
Another advantage of fMRI use is the possibility of defining the seizure spatially and temporally. Krings et al.  performed fMRI on a patient, who happened to experience a simple partial seizure; the seizure was associated with changes in MR signal in different regions, showing the spatiotemporal course of spreading. fMRI data correlated with EEG-determined seizure foci. Hence, it is possible to use fMRI not only to detect the cortical location of activations associated with the seizure, but also to define the epileptogenic focus in the originally activated area. The recent development of EEG-triggered fMRI allows interpretable electroen-cephalographic data to be recorded during MRI scanning. In this way, it is possible to combine the spatial resolution of MRI with the temporal resolution of elec-trophysiology in the seizure localization. EEG-linked fMRI acquisition is a promising technique in the field of epilepsy
fMRI and AVM
The presurgical evaluation of arteriovenous malformations (AVMs) is another interesting and controversial application of fMRI. They are the most common of cerebrovascular malformations and consist of a coiled mass of arteries and veins, without an intervening capillary network, lying in a bed formed by displacement rather than invasion of normal brain tissue. Functionally, they are direct arteriovenous communications causing a shunt of blood from the arterial to the venous side. The high flow volume shunted through an AVM fistula appears as „voids" within the structure in morphological MR images and may induce a decrease in cerebral perfusion pressure in the downhill artery .
The surgical importance of AVMs is related to their high probability of bleeding and giving epileptic crisis. In such situations, the localization of eloquent cortices near AVMs becomes important not only presurgically, but also during possible embolization procedures, because, when there is doubt that an AVM is close to eloquent tissue, particular care must be exercised to avoid devascularizing these functional areas.
The debate about the use of fMRI in AVMs revolves around the peculiar haemodynamics of this pathology. AVMs produce high velocity, low resistance blood-f ow and induce feeding artery hypotension and draining vein hypertension, with a potential net reduction in cerebral perfusion pressure in neighbouring territories. Chronic hypotension does not necessarily result in loss of neuronal function in brain tissues surrounding AVMs, but haemodynamic perturbations may reduce or impede the BOLD signal in adjacent eloquent cortex, obscuring activation where neuronal function may be present.
More specifically, there is a possible disagreement with respect to the presence or absence of significant activation within and around the nidus. The nidus represents the area, interposed between the distal segments of feeding arteries and the emerging proximal segments of draining veins, where arteriovenous shunting occurs. As revealed by histopathological findings, the nidus excludes intervening brain, whereas feeding and draining vessels are separated by brain parenchyma. Therefore, shunted blood within the nidus should not take part in metabolic changes occurring during neuronal activity, including oxygen consumption. Considering that the origin of the fMRI signal is the BOLD phenomenon, activation should not be measurable within the nidus of an AVM. The conflicting results in the literature may derive from the morphological difficulty in distinguishing the exact border of the nidus from the adjacent complex and variably dilated vessels on MR images. Intervening brain between distal feeding and proximal draining vessels could be mistaken for intranidal activation .
The above haemodynamic problems occur when there are severe flow anomalies; yet many patients have only moderate or any flow alterations at all. In these cases, a high correlation has been shown between fMRI mapping and electrocortical stimulation mapping .
Finally, Cannestra et al. propose the subdivision of MAVs into three groups on the basis of fMRI results. In group I (minimal risk), AVM and eloquent areas are disjoined by at least one gyrus free from activation; in group II (high risk) AVM and eloquent areas are intimately associated; in group III (indeterminate risk)
AVM and eloquent areas are adjacent to each other. Group I patients may undergo direct surgical excision of the AVMs solely on the basis of fMRI maps. Group II patients are considered inoperable and are referred for radiosurgery. In group III patients, eloquent areas are too close to the AVMs (less than 1 cm) to allow estimation of risk; these patients are considered candidates for intraoperative electrocortical stimulation .
fMRI and Other Pathologies fMRI is rapidly moving into the clinical setting, including being used for traumas, vascular diseases, inflammations, multiple sclerosis, Alzheimer disease, developmental disorders, learning disabilities and many other conditions .
One good example is the presurgical evaluation of a hydrocephalus case, which had a temporo-occipital cyst as an EEG documented source of epilepsy. The surgical question was the removal of the temporo-occipital cyst, in a patient with nearly normal full visual fields. fMRI revealed the existence of an eloquent area medial to the cyst, a result that documented a functional reorganization of the visual cortex. This way of presurgical-ly defining visual cortex plasticity called for a conservative resection of the temporo-occipital region, with sparing of the medial aspect of the cyst .
fMRI and Presurgical Risk
The presurgical evaluation of patients with cerebral lesions involves the evaluation of the risk of post-surgery sequelae. Of course it is imperative for the patients to know the kind of deficit they are going to meet, as well as the probability this deficit will actually occur. In other words, the methodological approach to the risk assessment should be qualitative and quantitative. The qualitative aspect examines which function is at risk of being damaged and refers to the location of eloquent areas concerning that function (e.g. motor cortex for motion, Wernicke's and Broca's areas for language, etc.). The quantitative aspect is far more difficult to evaluate. Many studies have investigated this problem (cf.  for review) and the resultant quantitative best parameter to evaluate this risk is the distance between eloquent areas and lesions. The outcome of such a kind of analysis gives the following resulting values: when the distance lesion-eloquent areas exceeded 2 cm, surgical resection was considered safe and no sequelae occurred in patients. As the distance decreased, the risk of deficits increased: when the value was between 1 and 2 cm, 33 % of patients showed postoperative deficits. Finally, when the distance was less than 1 cm, 50 % of patients experienced postoperative sequelae. Similar re sults were obtained by Haglund et al.  some years previously. These authors, by intraoperative cortical stimulation, showed no sequelae for distances over 2 cm, 17% sequelaefor distancesbetween 0.7and 1 cm, and 43 % sequelae for distances under 0.7 cm. Many authors (cf.  for review) also compared fMRI mapping of eloquent areas with results obtained by direct cortical mapping and a good spatial correlation between the two methods was shown.
These results indicate a reliability of fMRI not only in defining the anatomical locations of an explored function, but also in determining the presurgical risk. In this way, the patient are given reliable information on possible postoperative loss of function, making them clearly and fully aware at the moment of informed consent, and, at the same time, it is possible to set up a process of proper presurgical planning.
We received our 3 T GE Signa Excite MRI system in February 2004, but our experience with fMRI dates only from October 2004, when we received the stimulating apparatus. From October 2004 to June 2005, we performed fMRI on 27 patients with the following pathologies: 15 tumours, 4 AVMs, 4 cavernous angiomas, 2 dys-plasias, 1 Parkinson's disease and 1 aphasia. Of these patients, 12 did not undergo surgery, 2 because of non-surgical pathologies (aphasia and Parkinson) and the other 5 because fMRI showed eloquent areas strictly adjacent to the lesions. The remaining 15 patients underwent surgery. Again, of these, 7 did not show activation areas adjacent to the lesions and had no post-surgical sequelae (cf. e.g. Fig. 19.3), whereas the last 8 had eloquent cortices adjacent to the lesions. Of these, 3 (37.5%) experienced post-surgical sequelae (1 serious deficit and 2 moderate deficits, cf. e.g. Figs. 19.5,19.6). The above percentage values are in good agreement with the previously described values of presurgical risk (cf. 33% in ).
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