Current Medical Imaging - Volume 1, Issue 2, 2005

In recent years, a whole-brain unbiased objective technique, known as voxel-based morphometry (VBM), has been developed to characterise brain differences in vivo using structural magnetic resonance images. The present review provides a brief description of VBM and then focuses on exemplar applications in healthy and diseased subjects. The procedure involves normalising high-resolution structural magnetic resonance images to a standard template in stereotactic space. Normalised images are then segmented into gray and white matter and smoothed using an isotropic Gaussian kernel. Finally, a series of voxel-wise comparisons of gray and white matter in different groups of subjects are performed, using Random Field theory to correct for multiple comparisons. VBM has been useful in characterizing subtle changes in brain structure in a variety of diseases associated with neurological and psychiatric dysfunction. These include schizophrenia, developmental and congenital disorders, temporal lobe epilepsy and even cluster headache. In addition, VBM has been successful in identifying gross structural abnormalities, such as those observed in herpes simplex encephalitis, multiple sclerosis and Alzheimer's disease. Studies of normal subjects, on the other hand, have focussed on the impact of learning and practice on brain structure. These studies have led to the finding that environmental demands may be associated with changes in gray and white matter. For instance, it has been reported that the structure of the brain alters when human beings learn to navigate, read music, speak a second language and even perform a complex motor task such as juggling. We conclude the present review by discussing the potential limitations of the technique.

The last eight years have seen a rapid expansion in the number of functional Magnetic Resonance Imaging (fMRI) studies of the emotions, examining the role of the amygdala in healthy human emotion function as well as in psychiatric and neurological disorders such as depression, autism, anxiety disorders and schizophrenia. Amongst widely divergent results, the central findings of these studies are reviewed, as well as the most important unresolved questions. The location of central elements of the limbic system, of which the amygdala is a part, makes it a challenging area to study with fMRI. The problems besetting the region are reviewed: signal loss and image distortion in Echo Planar Imaging and artefacts arising from physiological fluctuations, head motion and draining veins. We describe general approaches to mitigating these problems and which of those we find to be most useful. An illustrative example from our lab is presented to indicate the typical progression of an emotion fMRI session and to allow discussion of the strategies employed which enable robust amygdala function to be charted in single subjects and groups. We conclude by examining the prospects for technical improvement and clinical applications.

Although extensive surgical resection represents the first treatment in brain tumors, the risk of postoperative sequelae still persists. Consequently, neurosurgical procedure should be adapted to (1) the behavior of the tumor (2) its cerebral location (3) the individual functional organization of the brain (4) the dynamic interactions between these parameters. I first review the advantages and limitations of the non-invasive metabolic (SPECT, PET, SRM, DWI), functional (PET, fMRI, NIRS, MEG) and anatomical (DTI) neuroimaging techniques, which contribute to select the surgical indications and to plan the procedure. In addition, intraoperative electrical stimulation can be used during the resection, if necessary on awake patient when cognitive functions need to be mapped, in order to detect cortico-subcortical structures functionally essential. Second, the applications of these methods for tumor surgery are considered, with the following interests: - to understand the individual cortical functional organization before the beginning of the resection; - to improve the knowledge of the pathophysiology of brain areas frequently involved by tumor; - to map the subcortical structures all along the resection, allowing a study of the anatomo-functional connectivity; - to study the mechanisms of on-line functional reorganization, using repeated stimulations; - to perform the resection according to functional boundaries, allowing to optimize the quality of lesion removal while minimizing the risk of postoperative sequelae. Finally, the results of pre-, intra- and post-operative functional mappings can be combined, to better understand both short-term and long-term plasticity mechanisms associating functional cortical reshaping and connectivity changes - due initially to the tumor growth, then to its resection.

Functional and structural imaging studies of major depressive illness reported over the past decade are reviewed. It is concluded that while various prefrontal and temporal brain regions are often reported as being abnormal, interpretation of such findings is limited due to lack of understanding of normal function. This leads to a discussion of what is known of normal function. It is concluded that in animals, these brain regions correspond to the neural substrate for emotional learning, representation of the rewarding and aversive aspects of stimuli, and associated behavioral response. Imaging studies, which investigate reward based learning in humans appear consistent. Additionally however, these brain regions may be most active in healthy humans experiencing emotion. A large meta-analysis exploring this issue is discussed. The link between normal human emotions and reinforcers is then reviewed, followed by a discussion of the clinical features of depressive illness, in the light of the hypothesis that depressive illness is a disorder of emotional learning. Formal mathematical theories of emotional learning all include a predictive error term, formed by the difference between future predicted reward or punishment and the actual outcome. Extensive experimental evidence of the existence of predictive error signals in animals, and more recently in imaging studies of healthy humans, is reviewed. This is followed by a discussion of a study reporting abnormal predictive error signals in depressed patients, which tested the hypothesis that depressive illness is a disorder of emotional learning. Finally, existing diverse treatments for depressive illness are considered from the perspective of emotional learning mechanisms. A number of studies are suggested, to clarify understanding of the mechanisms of effective treatments for depressive illness.

The transcranial Doppler ultrasonography (TCD) was introduced into the practice of medicine in 1986 and has been used extensively in a variety of in- and out-patient settings. TCD provides a quantitative assessment of cerebral hemodynamics and measures linear cerebral blood flow velocity (CBFV) in cm/sec. Due to its noninvasiveness and easy applications, TCD examinations have gained an important role in the very early phase, as well during the repetitive assessment of cerebrovascular diseases. This has led to a broad application of TCD in out-patients, in-patients, emergency and intraoperative settings. TCD allows interrogation of the cerebral circulation in a safe, noninvasive, repeatable and cost-effective manner. TCD within 24 hours of symptoms onset improves the early accuracy of stroke subtype diagnosis in patients with large artery atherosclerosis. Early detection may affect therapeutic strategies in patients with acute cerebral ischemia or extra- or intracranial lesions (symptomatic or asymptomatic). The unique ability of TCD to monitor CBFV continuously and detect the time course of changes is invaluable in the Intensive Care Unit, during carotid surgery, certain endovascular procedures, etc. TCD helps guide decision making to prevent or minimize the effects of stroke, brain injury and it is a significant addition to the armamentarium of medicine.

Transcranial Doppler (TCD) with a 2 MHz pulsed-wave diagnostic ultrasound beam can facilitate the diagnosis of cerebral arterial occlusion and can improve outcomes. First, it can be used to identify the presence and location of an obstructive intracranial thrombus confirming the vascular origin of patient neurological symptoms. Second, it provides real-time bedside monitoring of thrombolysis. And finally, it augments residual flow and speeds up thrombolysis allowing patients to recover from stroke more rapidly and completely. We aim to review the latest applications and benefits of TCD in the acute phase of ischemic stroke.

Parathyroid imaging has been widely used for the identification and localization of abnormal parathyroid adenomas in patients with suspected primary hyperparathyroidism and for preoperative and reoperative localization. However, recently developed methods of functional imaging, like 99mTc-sestamibi parathyroid scan combined with routine anatomic procedures, provide additional quantitative and qualitative information on various types and stages of parathyroid hyperplasia which is the common presentation of secondary hyperparathyroidism. This kind of information could not only prove useful in preoperative diagnosis, but also in the selection of medical or surgical therapeutic alternatives in secondary hyperparathyroidism patients. Our group found a significant correlation between 99mTcsestamibi uptake and parathormone blood levels but no correlation was found with other determinants of hyperparathyroidism. This finding demonstrates that scintigraphy accurately reflects the gland activity independently from other biochemical parameters that could be influencing gland secretion. It is reasonable to assume that better preoperative information will ease the detection of hyperplastic glands and reduce operative time and surgical trauma. This review discusses the role of non-invasive imaging modalities prior to surgery, and also in the clinical management of patients with secondary hyperparathyroidism.