Current Medical Imaging - Volume 2, Issue 1, 2006

Two observations emerge from a review of the articles contained in this issue of CMIR. The first and perhaps most important is the remarkable growth in diagnostic technology. PET imaging has increased in utilization during the past several years so that it is now a part of the state-of-the-art of cancer care. The increased availability of combined PET/CT imaging has greatly fostered its growth and increased the specificity and accuracy of the technology. During the same time interval, faster and faster multi slice computed tomography devices have become available so that at the present time a 16 slice CT machine is pretty much the state-of-the-art, with 32 slice machines moving into the clinical area and 64 slice machines not far behind. The ultimate cardiac approach on the horizon appears to be the combination of a 64 slice CT with a PET machine so that patients would be able to have non-invasive coronary angiography performed at the same sitting with physiologic studies demonstrating perfusion and leading to decisions regarding cardiac intervention with no need for a cardiac cath. Of course, as this technology becomes more and more refined, there is an unavoidable increase in the cost of medical diagnosis. We have yet to learn the balance between physical examination, imaging technology and patient care. Unfortunately too many physicians move quickly to diagnostic studies without a careful intervening medical history and physical examination. That said, the other observation is that in this issue, which contains 13 articles, 8 are directly related to studies of the brain. It is remarkable that although a remarkable amount of work has been directed towards the study of the brain utilizing CT, MRI, and PET, the roles of these modalities in clinical medicine do not reflect volume of physiologic research. MR and CT have certainly become standard techniques for evaluating the brain but as demonstrated in these articles much of the information derived is still in the research sphere. Even more impressive is the general lack of utilization of PET in studies of brain disease while it has played a profound role in defining diseases such as Alzheimer's disease, multi infarct dementia, and other serious brain afflictions. It is evident from a review of these articles that diagnostic technology is improving at a logarithmic rate. It is also evident from the large number of research publications in the various areas that the movement from the laboratory to clinical medicine continues to lag. We are faced with an explosive growth in diagnostic methodology during the next decade. How this will impact on financing of medical care and on the algorithms for diagnosis of disease is something that will be a painful evolution both politically and economically based with a revolution medically and scientifically.

During the last two decades, functional brain imaging using positron emission tomography (PET) has advanced elegantly, and steadily gained importance in the clinical and research arenas. Significant progress has been made by different scanner manufacturers and research groups in the design of dedicated high-resolution three-dimensional (3-D) PET units; however, emerging clinical and research applications of functional brain imaging promise even greater levels of accuracy and precision and therefore, impose more constraints with respect to the intrinsic performance of the PET tomograph. Continuous efforts to integrate recent research findings for the design of different geometries and various detector/readout technologies of PET scanners have become the goal of both the academic community and nuclear medicine industry. As PET has become integrated into clinical practice, several design trends have developed; with systems now available with a spectrum of features, from those designed for "low cost" clinical applications to others designed specifically for very high-resolution research applications. There is also a continual upward revision and refinement in both hardware and software components for all of these systems. Software- and hardware-based correlation between anatomical (x-ray CT, MRI) and physiological (PET) information is a promising research field and now offers unique capabilities for the medical imaging community and biomedical researchers. One of the main advantages of dual-modality PET/CT imaging is that PET data are intrinsically aligned to anatomical information from the x-ray CT without the use of external markers or internal landmarks, thus providing a reliable estimate of the attenuation map to be used for attenuation and scatter correction purposes. On the other hand, combining PET with MRI technology is scientifically more challenging owing to the strong magnetic fields. Nevertheless, significant progress has been made resulting in the design of a prototype small animal PET scanner coupled to three multichannel photomultipliers via optical fibers, so that the PET detector can be operated within a conventional MR system. Thus, many different design paths have been and continue to be pursued in both academic and corporate settings, that offer different trade-offs in terms of their performance. It still is uncertain which designs will be incorporated into future clinical and research systems, but it is certain that technological advances will continue and will enable new quantitative capabilities in brain PET imaging. This paper briefly summarizes state of the art developments in dedicated brain PET instrumentation. Future prospects will also be discussed.

Inferences about brain function, using functional neuroimaging data, require models of how the data were derived. A variety of models are used in practice that range from conceptual models of functional anatomy to nonlinear mathematical models of hemodynamic responses (e.g. as measured by functional magnetic resonance imaging, fMRI) and neuronal responses. In this review, we discuss the most important models used to analyse functional imaging data and demonstrate how they are interrelated. Initially, we briefly review the anatomical foundations of current theories of brain function on which all mathematical models rest. We then introduce some basic statistical models (e.g. the general linear model) used for making classical (i.e. frequentist) and Bayesian inferences about where neuronal responses are expressed. The more challenging question, how these responses are caused, is addressed by models that incorporate biophysical constraints (e.g. forward models from the neural to the hemodynamic level) and/or consider causal interactions between several regions, i.e. models of effective connectivity. Some of the most refined models to date are neuronal mass models of electroencephalographic (EEG) responses. These models enable mechanistic inferences about how evoked responses are caused, at the level of neuronal subpopulations and the coupling among them.

During the past years brain imaging techniques like positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) became more and more important for gaining new insights into processes of and circuits for memory encoding and retrieval. These findings also had a great impact on a better understanding of memory dysfunctions and their underlying brain mechanisms. In the present review, data on memory dysfunctions are analyzed separately according to whether they are of an organic, or a psychiatric psychogenic etiology. Studies examining patients with various forms of amnesia and dementia, for whom functional brain imaging data were available, indicate early functional brain changes. These early changes differ from subsequent structural brain changes and therefore support the clinical and diagnostic use of functional brain imaging techniques in memory disturbances. Furthermore, research outcomes from patients suffering from psychogenic amnesias (dissociative amnesias) and psychogenic fugue conditions are summarized. Finally, differences and similarities between organic amnesia and psychogenic amnesia are discussed with regard to the present literature and exemplified with two single cases from our lab.

Functional neuroimaging has provided a new view of the activity in the human cortex. The understanding of the relationship between functional signals, particularly functional MRI, clinical disorders and cognitive functions has increased. This article reviews selected contributions of positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) with a focus on their interest to better understand visual cognition, hemispheric specialization, and cerebral plasticity. Future directions of functional neuroimaging research are proposed, with the emphasis that the most complete conclusions are drawn by convergence of research from functional neuroimaging, neurophysiological, and lesion studies. We also briefly mention the emerging role of TMS, as a tool to simulate, study and understand the dynamic course of deficits observed after a cortical lesion in 'virtual neuropsychology'.

During the last five years, neuroimaging techniques such as Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI) appeared as new tools to study the neural correlates of human male sexual arousal (SA). In this paper, some of the main methodological aspects of these studies will be summarized, including the participants, the way to induce sexual arousal within the scanner and the different types of analyses performed. In the second part, some of the cerebral areas that have been related to sexual information processing are presented. Among others, cerebral areas that have been related to cognitive processes involved in SA are first presented: the orbitofrontal cortex and parietal lobules. We then focus on recent studies that concurrently measured cerebral and penile responses by plethysmography. Some cerebral areas where significant correlations were found between the hemodynamic cerebral and the plethysmographic signals are presented. Finally, as the use of different penile plethysmographic methods were referred to in the literature, we consider the prospects of their use for the study of the neural correlates of human male SA.

The clinical use of ultrashort echo time (UTE) pulse sequences for imaging tissues or tissue relaxation components with short T2s is described. Tissues are divided into those with a majority of short T2 components and those with a minority. Disease processes which increase or decrease the signal from short T2 components are described. Features of the basic physics are described including the fact that when the radiofrequency pulse duration is of the order of T2, rotation of tissue magnetization less than the specified flip angle. The basic UTE pulse sequence with its half excitation pulses and radial imaging from the center of k-space is described together with options that suppress fat and/or long T2 components. Features of the imaging of cortical bone, tendons, ligaments, menisci and periosteum are illustrated. Possible future developments are outlined.

Accurate segmentation of magnetic resonance (MR) images of the brain is of interest in the study of many brain disorders. In this paper, we provide a review of some of the current approaches in the tissue segmentation of MR brain images. We broadly divided current MR brain image segmentation algorithms into three categories: classificationbased, region-based, and contour-based, and discuss the advantages and disadvantages of these approaches. We also briefly review our recent work in this area. We show that by incorporating two key ideas into the conventional fuzzy cmeans clustering algorithm, we are able to take into account the local spatial context and compensate for the intensity nonuniformity (INU) artifact during the clustering process. We conclude this review by pointing to some possible future directions in this area.

Approximately half of all strokes result in moderate-to-severe disability, making stroke the leading cause of long-term disability in North America. Functional magnetic resonance imaging (fMRI) has emerged as a powerful tool to investigate functional reorganization, temporary or permanent, during the recovery of motor and cognitive functions following stroke, as a means to potentially predict patient outcome and guide rehabilitation. Recently, fMRI studies of stroke recovery have been moving towards a clinical focus, with increased emphasis on longitudinal investigations of recovery. In addition, the integration of fMRI with other imaging modalities such as electroencephalography (EEG) and near-infrared (NIR) diffuse optical tomography is becoming increasingly important to further investigate the spatiotemporal evolution of brain function following stroke. This article will review the literature of longitudinal studies of motor and cognitive recovery using fMRI, as well as discuss issues regarding the possible implementation of fMRI for longitudinal studies of stroke recovery in individual patients.

The pulsation of the cerebrospinal fluid (CSF) has fascinated investigators of the intracranial physiology since it was first documented by invasive CSF pressure measurements. Advances in dynamic Magnetic Resonance Imaging (MRI) now enable visualization of and quantitation the CSF flow dynamics and has contributed to our understanding of the origin of CSF pulsation and its relation to the pulsatile blood flow. This, in turn, has led to the development of a noninvasive method for measurement of intracranial compliance and pressure by MRI. This article reviews the neurophysiologic and hydrodynamic principles that are the basis of the method, it describes the implementation of the method and validation studies to date with a non-human primate animal model, computer simulations, healthy human subjects and patients. The article further reviews the application of this method to study the effect of body posture on the cerebral physiology in humans through the relationships between blood and CSF flow dynamics. Finally, recent results from the application of the method in Chiari Malformations (CM) are briefly presented as an example of a potential clinical application of this methodology. The application to CM provided, for the first time, evidence of the important role intracranial compliance plays in the pathophysiology of this poorly understood disorder. The potential diagnostic value of an MRI-based measurement of ICP for other neurological problems is discussed.

Magnetic Resonance Imaging (MRI) machines are invariably grouped according to their main magnetic field strength. Yet far more important to their overall performance are their gradient coils. For it is these that determine the limitations of the crucial parameters, TE, image speed, even the acoustic noise produced, in every imaging sequence. To some degree, the gradients even determine what imaging sequences are possible of the system. For this reason it is vitally important that every purchaser and user of MRI machines have at least some grounding and background of gradient performance. To that end the following paper reviews the historic development, the current state of the art and future directions of what is still an active ongoing research program to improve the performance of these vital components of MRI machines.

During the past few years, Multi-Slice Computed Tomography (MSCT) has emerged as a rapidly progressing technique with a high potential for non-invasive angiography. Recent studies using the latest 16-slice technology have demonstrated that the technique can detect coronary artery lesions with sensitivities and specificities of approximately 92% and 95%, respectively. In particular, the negative predictive value of the technique is very high, suggesting that MSCT could play an important role in excluding coronary artery disease prior to more invasive procedures. Besides noninvasive coronary angiography, several other potential applications of MSCT exist, including left ventricular function analysis and evaluation of pulmonary vein anatomy. Although data on these topics are still limited, initial results appear very promising. Thus, MSCT is likely to become a diagnostic modality integrated in clinical cardiology. The purpose of the present review is to provide an overview of the potential clinical applications of cardiac MSCT with emphasis on non-invasive coronary angiography.

Magnetic Resonance Angiography (MRA) with intravenous paramagnetic agent has recently evolved as an accurate non invasive method, for the imaging of the aorta and its major branches, the carotid, the renal and pelvic arteries. The first report of contrast enhanced MRA was published at 1993. Recently a new method was developed, employing the motion of the MR table, during the examination (Moving bed - bolus chase MRA) which permits the imaging of the total length of the abdominal aorta down to the plantar arches. In patients with critical ischemia, it is critical to visualize the arteries beyond the trifurcation as well as the plantar arch, in order to decide whether to perform distal bypass or to amputate. However, transcatheter angiography commonly cannot depict the patency of a small caliber vessel, beyond the occlusion (runoff vessel). This vessel is called angiographically occult vessel and its depiction is critical for the surgical anastomosis. MRA is capable to detect very small amounts of paramagnetic agent within the vessel lumen, thus enabling the depiction of small caliber vessels. Nevertheless some problems need special attention, foremost of which is the early venous filling (venous contamination), occuring commonly in the diabetic patient population. The main advantages of MRA include the absence of ionizing radiation, and the avoidance of nephrotoxic contrast media.

Ultrasonic elasticity imaging is a promising new tool for breast cancer diagnosis and management. Ultrasound is applied to sense small local tissue deformations noninvasively to image stiffness and thus exploit the large intrinsic stiffness contrast generated during the progression of many diseases in vivo. This paper briefly reviews several related approaches to breast elasticity imaging to explain some of the observed variability in breast imaging results. Preliminary clinical results from a population of 13 patients with small and nonpalpable breast lesions obtained with a low noise elasticity imaging algorithm developed in our group are then reported. All the benign lesions exhibited normal elasticity ranges. About half of the malignant lesions were undetected with elasticity imaging most likely because of their small size (<7mm) or softening from the addition of fatty-replaced tissue. Other malignant lesions were clearly identified as areas with extreme elasticity values compared to their surroundings. We observed that some malignant lesions did not exhibit any desmoplasic stiffening while others showed an uncommon softening. It is clear that by broadening the study population to include small and nonpalpable lesions, we see much variability in elasticity image findings.