Current Medical Imaging - Volume 3, Issue 2, 2007

The last quarter century has witnessed the introduction of a variety of powerful techniques that have allowed visualization of organ structure and function with exquisite detail. This in turn has brought about a true revolution in the day-to-day practice of medicine. There are six articles in this issue, related to the MRI for cartilage and disc, oncology, brain function and dementia, the MR spectroscopy for breast and ovary cancer, and the optical spectroscopy for cerebral blood flow. Although MRI has become the most accurate test for depicting abnormal anatomy, there is no agreement on the diagnostic value of morphology alone. If the natural history of a disease is not clearly understood, and if there is little consensus regarding the use of diagnostic tests, the risk of misdiagnosis is high. Degenerative disc disease is debilitating, costly, and one of the most complex conditions to manage. MRI has demonstrated alterations in material properties (mainly glycosamineoglycans, water and collagen) of hydrated cartilages and also intervertebral disc tissues during the disease developments. The long term goal would develop techniques to detect changes of early degeneration of cartilages and discs. It was found that contrast-enhanced MRI improved lesion detection, delineation, and specificity. The major factors influencing lesion detection include lesion contrast, size, location, and type. Dynamic contrast enhanced MRI (DCE-MRI) enables the quantitative assessment of tumor status using blood flow, vessel permeability, and tissue volume fractions extracted from each voxel or region of interest. Functional MRI has been widely used to evaluate brain response for extensive number of different tasks, and primarily intended for the assessment of physiologic phenomena, such as changes in blood flow and perfusion to an organ or diseased tissue. I remains unclear which brain region is relevant for the principal cognitive/behavioral function and which areas are activated either ws a result of the additional cognitive function or as consequence of brainconnectivity. The recent conbination of transcranial magnetic stimulation and functional MRI has shown to be a promising tool to clarify this dilemma. With the current trend towards increasing longevity of life, the prevalence of dementia will become higher during the next few decades. Dementic illness imposes significant burdens on the society, health care and economy. Neurochemical imaging is one of the most established molecular imaging technique. There have been tremendous efforts to develop radioligands specific to each neurochemical system. Investigational applications of neurochemical imaging indementing disorders are extensive. These investigations have provided important insights into disease processes inliving human patients. Frontotemporal decrease of the activity on functional imaging is an independent marker of the frontal variant of frontotemporal dementia. MR spectroscopy (MRS) is increasingly receiving more attention from oncologists, neuropsychiatrists, radiologists, and other clinicians. The choline peak from proton spectra is a constitution of the phospholipids metabolism of cell membrane and thus reflects a membrane turnover. It is a precursor of acetylcholine and phosphatidylcholine and therefore increased choline probably suggests increased membrane synthesis or an increased number of cells such as seen in active tumors. Efforts are addressed to evaluate effectiveness and potential use of MRS and choline-based PET in cancer diagnosis. Optical imaging is a very powerful molecular imaging probe, but it does not lend itself well to examining biologic processes. Tradionally it has had physiological limitations in visualizing deel structures or lesions. However, new-generation near infrared spectroscopy (NIRS) instrumentation with depth-resolved technologies and invasive NIRS probes will provide unique physiologic informations including cerebral blood flow.

The aim of this review is to present the different stages, from geometrical to mechanical data, in the development of sensitive and non-invasive MRI techniques for describing alterations in material properties of cartilage and intervertebral disc tissue with disease. The first section summarizes some MRI techniques used to quantify the geometrical changes in cartilage and intervertebral disc tissue that appears with diurnal activity, specific movements or loadings, or else with various diseases. The second section describes the MRI techniques used to evaluate the biochemical composition of cartilage and intervertebral disc tissue, mainly the glycosaminoglycans (GAGs) and water contents, and the collagen organization. The third section describes the MRI techniques used to quantify the mechanical and structural properties of bone tissue. The last section presents the new MRI techniques used to evaluate the mechanical properties of hydrated cartilage and intervertebral disc tissue. More studies highlighting the ability of MRI to describe the fluid phase behavior within the cartilage or intervertebral discs tissue should be perform. The long term goal would be to develop sensitive and non-invasive clinical techniques for the early detection of the changes in the mechanical properties of both solid and fluid phases that appear with degeneration.

Dynamic contrast enhanced MRI (DCE-MRI) enables the quantitative assessment of tumor status and has found application in both pre-clinical tumor models as well as clinical oncology. DCE-MRI requires the serial acquisition of images before and after the injection of a paramagnetic contrast agent so that the variation of MR signal intensity with time can be recorded for each image voxel. As the agent enters into a tissue, it changes the MR signal intensity from the tissue to a degree that depends on the local concentration. After the agent is transported out of the tissue, the MR signal intensity returns to its' baseline value. By analyzing the associated signal intensity time course using an appropriate mathematical model, physiological parameters related to blood flow, vessel permeability, and tissue volume fractions can be extracted for each voxel or region of interest. In this review we first discuss the basic physics of this methodology, and then present technical aspects of how DCE-MRI data are acquired and analyzed. We also discuss appropriate models of contrast agent kinetics and how these can be used to elucidate tissue characteristics of importance in cancer biology. We conclude by briefly summarizing some future goals and demands of DCE-MRI.

Functional magnetic resonance imaging (fMRI) has been widely used to evaluate the brain's response to an extensive variety and number of different tasks; however, because many of these paradigms are complex, they stimulate a broad neural network encompassing several brain regions. Therefore, it remains unclear which brain region is relevant to the principal cognitive/behavioral function that is being studied, and which areas are activated either due to the additional cognitive function required to complete the task, or as a consequence of brain connectivity. The recent combination of transcranial magnetic stimulation (TMS) with fMRI holds promise for clarifying this dilemma. Using a pulse of magnetic field, TMS can non-invasively stimulate a specific brain region, thereby allowing brain activity to be manipulated as an independent variable, while, based upon the Blood Oxygenation Level Dependence (the BOLD effect), fMRI can evaluate the brain's response to this localized stimulus, highlighting the functional network directly associated with the stimulated site.

The frontal variant of frontotemporal dementia (fvFTD) is clinically characterized by a disruption of the social behaviour. Frontotemporal decrease of activity on functional imaging is an independent marker of the disease. Principal component analysis of cerebral functional images reveals one ensemble comprising both frontal lobes, and two lateralized clusters comprising temporal and subcallosal frontal regions. Executive dysfunction and verbal difficulties are shown to interact in fvFTD, and they are related to large scale frontal and temporal neural networks in the disease. The neural substrate of the memory impairments in patients with fvFTD is heterogeneous, since correlations were observed with frontal activity, but also with medial temporal atrophy. Behavioural changes are the hallmarks of fvFTD. Apathy is consistently related to frontal involvement, while disinhibition occurs in patients with predominant posterior orbitofrontal and temporal involvement. The consequences of lateralized brain lesions remain a matter of debate, since impulsive and compulsive behaviour was evenly related to right or left temporal involvement in fvFTD. Those patients know social rules, but they are impaired in assessing the importance of social transgressions and in recognizing emotions. Processing transgressions of social norms results in a complex activation of medial prefrontal, orbitofrontal and temporal regions in control populations. The variable decrease in these regional activities observed in different fvFTD patients would explain their complex, individual social disturbance.

Elevated contents of choline phospholipid metabolites are typically detected by nuclear magnetic resonance spectroscopy (MRS) in human and animal tumors. An increase in the intensity of the 1H-MRS profile of total cholinecontaining compounds (tCho, 3.2 ppm) is today considered as a common feature in different types of cancer, beyond their otherwise wide phenotypic variability. This finding fostered investigations on the molecular mechanisms underlying the observed spectral changes and on correlations between aberrant phospholipid metabolism and tumor progression. At the clinical level, efforts are addressed to evaluate effectiveness and potential use of in vivo localized MRS and choline-based positron emission tomography (Cho-PET) in cancer diagnosis. Aims of this article are: a) to overview recent advances in the identification of biochemical pathways responsible for the altered 1H-MRS tCho profile in breast and ovary cancer cells, as a basis for interpreting in vivo MR spectra and enhanced uptake of radiolabeled choline in PET; b) to summarize recent developments of in vivo 1H-MRS methods in breast cancer diagnosis; c) to discuss the potentialities of complementing current diagnostic modalities with noninvasive MRS and Cho-PET methods to monitor biochemical alterations associated with progression, relapse and therapy response in ovary cancer.

Early detection and treatment of cerebral ischemia to prevent further neurological damage in patients with severe brain injuries, such as in trauma and stroke patients, is one of the most important issues in Neurocritical Care. Our own clinical experiences in treatment of patients with severe ischemic stroke and subarachnoid hemorrhage have shown that the available methods to monitor cerebral hemodynamics and oxygenation are insufficient with regard to detection of secondary ischemic events. The established methods for bedside monitoring of cerebral blood flow (CBF) and cerebral oxygenation are difficult to perform clinically, involve radioactive radiation, are invasive or require the patient to be transported, thus involving potentially high risks. Transcranial Doppler sonography produces indices that can be related to changes in CBF and cerebral oxygenation but does not measure actual flow rates. During recent years, near infrared spectroscopy (NIRS) was further developed and supplemented with the indocyanine green (ICG) dye dilution mode for bedside monitoring of CBF. The NIRS ICG dye dilution technique is a promising method for serial bedside CBF measurements in the environment of the intensive care unit. The NIRS method with optodes on the skin has the advantage of being non invasive, does not require the patient to be transported and provides data at the bedside within minutes. Preliminary data in a limited number of volunteers indicate that CBF measurements obtained by NIRS ICG dye dilution technique are in agreement with corresponding values obtained by perfusion-weighted MRI. More patient-validated data by correlating the measurement values with clinical events and comparing them with standard methods are needed. For the accuracy of absolute measurements and in order to quantify the individual extracerebral pathlengths as well as to allow appropriate correction to be made for extracerebral dead space tissue further modelling based on patients data is required. New-generation NIRS instrumentation, implementing spatially resolved spectroscopy (SRS), depth-resolved technologies and invasive NIRS probes will give the opportunity to reduce or eliminate extracerebral contamination and will provide some unique physiological information for NIRS technology. To calculate the influence of extracerebral contamination comparative measurements can be performed using noninvasive NIRS probes on the scalp and invasive probes for NIRS and intracranial pressure (ICP) monitoring. Combined monitoring of ICP and NIRS will be of special clinical value in patients with severe stroke, subarachnoid hemorrhage and head trauma, already provided with ICP probes for treatment of intracranial hypertension and being especially at risk for secondary ischemic brain damage.