There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

Pattern Recognition and Machine Learning

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Aims To develop and validate a non-invasive method for measuring myocardial iron in order to allow diagnosis and treatment before overt cardiomyopathy and failure develops.Methods and Results We have developed a new magnetic resonance T2-star (T2*) technique for the measurement of tissue iron, with validation to chemical estimation of iron in patients undergoing liver biopsy. To assess the clinical value of this technique, we subsequently correlated myocardial iron measured by this T2* technique with ventricular function in 106 patients with thalassaemia major. There was a significant, curvilinear, inverse correlation between iron concentration by biopsy and liver T2* (r=0(.)93, P <0(.)0001). Inter-study cardiac reproducibility was 5(.)0%. As myocardial iron increased. there was a progressive decline in ejection fraction (r=0(.)61, P <0(.)001). All patients with ventricular dysfunction had a myocardial T2* of < 20 ms. There was no significant correlation between myocardial T2* and the conventional parameters of iron status, serum ferritin and liver iron. Multivariate analysis of clinical parameters to predict the requirement for cardiac medication identified myocardial T2* as the most significant variable (odds ratio 0(.)79, P <0(.)002).Conclusions Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment. Myocardial iron content cannot be predicted from serum ferritin or liver iron, and conventional assessments of cardiac function can only detect those with advanced disease. Early intensification of iron chelation therapy, guided by this technique. should reduce mortality from this reversible cardiomyopathy. (C) 2001 The European Society of Cardiology.

Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload

Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

In Vivo Endoscopic Optical Biopsy with Optical Coherence Tomography

Perfusion is a crucial physiological parameter for tissue function. To obtain perfusion-weighted images and consequently to measure cerebral blood flow (CBF), a newly developed flow-sensitive alternating inversion recovery (FAIR) technique was used. Dependency of FAIR signal on inversion times (TI) was examined; signal is predominantly located in large vessels at short TI, whereas it is diffused into gray matter areas at longer TI. CBF of gray matter areas in the human brain is 71 +/- 15 SD ml/100 g/min (n = 6). In fMRI studies, micro- and macrovessel inflow contributions can be obtained by adjusting TIs. Signal changes in large vessel areas including the scalp were seen during finger opposition at a TI of 0.4 s; however, these were not observed at a longer TI of 1.4 s. To compare with commonly used BOLD and slice selective inversion recovery techniques, FAIR and BOLD images were acquired at the same time during unilateral finger opposition. Generally, activation sites determined by three techniques are consistent. However, activation of some areas can be detected only by FAIR, not by BOLD, suggesting that the oxygen consumption increase couples with the CBF change completely. Relative and absolute CBF changes in the contralateral motor cortex are 53 +/- 17% SD (n = 9) and 27 +/- 11 SD ml/100 g/min (n = 9), respectively.

Perfusion imaging by a flow-sensitive alternating inversion recovery (FAIR) technique: application to functional brain imaging.

The continuous technological progress of magnetic resonance imaging (MRI), as well as its widespread clinical use as a highly sensitive tool in diagnostics and advanced brain research, has brought a high demand for the development of magnetic resonance (MR)-compatible robotic/mechatronic systems. Revolutionary robots guided by real-time three-dimensional (3-D)-MRI allow reliable and precise minimally invasive interventions with relatively short recovery times. Dedicated robotic interfaces used in conjunction with fMRI allow neuroscientists to investigate the brain mechanisms of manipulation and motor learning, as well as to improve rehabilitation therapies. This paper gives an overview of the motivation, advantages, technical challenges, and existing prototypes for MR-compatible robotic/mechatronic devices.

Magnetic resonance-compatible robotic and mechatronics systems for image-guided interventions and rehabilitation: a review study.

The combination of contrast enhanced magnetic resonance imaging (MRI) and MR-guided subcutaneous core biopsy can be used as a robust approach for the diagnosis and treatment of breast cancer. MRI provides the means to accurately position and monitor interventional procedures such as biopsy, removal of tissue or other transcanular procedures. MRI may also be used in this invention to position and monitor the progress of breast conserving therapies (BCT), such as laser photo-ablation, cryoablation and localized hyperthermia. The general practice of this invention is to provide a remotely controlled apparatus for MR-guided interventional procedures in the breast. The apparatus allows the practice of a method that provides flexibility in conditioning the breast, i.e. orientation and degree of compression, and in setting the trajectory of the intervention. To that end, a robust conditioning/positioning device, fitted with the appropriate degrees of freedom, enhances the efficacy and efficiency of breast interventions by providing the flexibility in planning and executing an appropriate procedure strategy that better suits interventional procedures, either those in current use or yet to be developed. The novelty and potential commercial success of the device originates from its high maneuverability to set and perform the procedure strategy and its adaptability to accommodate an array of interventional probes. Remote control of this device can allow planning the operation and performing the relevant tasks in a short period, for example, within the contrast window provided by a single injection of a contrast agent, and this feature can be operator-independent.

MRI-guided interventional mammary procedures

The objective of this work was to develop a robotic device to perform biopsy and therapeutic interventions in the breast with real-time magnetic resonance imaging (MRI) guidance. The device was designed to allow for (i) stabilization of the breast by compression, (ii) definition of the interventional probe trajectory by setting the height and pitch of a probe insertion apparatus, and (iii) positioning of an interventional probe by setting the depth of insertion. The apparatus is fitted with five computer-controlled degrees of freedom for delivering an interventional procedure. The entire device is constructed of MR compatible materials, i.e. nonmagnetic and non-conductive, to eliminate artifacts and distortion of the MR images. The apparatus is remotely controlled by means of ultrasonic motors and a graphical user interface, providing real-time MR-guided planning and monitoring of the operation. Joint motion measurements found probe placement in less than 50 s and sub-millimeter repeatability of the probe tip for same-direction point-to-point movements. However, backlash in the rotation joint may incur probe tip positional errors of up to 5 mm at a distance of 40 mm from the rotation axis, which may occur for women with large breasts. The imprecision caused by this backlash becomes negligible as the probe tip nears the rotation axis. Real-time MR-guidance will allow the physician to correct this error Compatibility of the device within the MR environment was successfully tested on a 4 Tesla MR human scanner

Design of an MRI-compatible robotic stereotactic device for minimally invasive interventions in the breast.

Based on the major innovations in ultrafast magnetic resonance (MR) imaging in recent years, myocardial perfusion imaging with MR has become the focus of many investigators. Two major approaches to myocardial perfusion imaging involve either exogenous or endogenous contrast agents. For the first category of perfusion experiments, we review the characteristics of the common contrast agents and MR techniques for experimental and clinical first-pass studies and in particular address the question of extracting quantitative estimates for myocardial blood flow (milliliters per minute per gram) and volume (milliliters per gram). We demonstrated quantitative perfusion analysis using intravascular relaxation agents and heavily T1-weighted ultrafast gradient echo sequences. Signal time curves need to be transformed to content time curves and the resulting residue functions were analyzed with a multiple-pathway, axially distributed perfusion model. These preliminary results suggest that quantitative assessment of myocardial perfusion is feasible, but additional studies should provide further confidence for this novel MR approach. The exact sensitivity and specificity of MR first-pass imaging in conjunction with extracellular contrast agents in patient studies and its diagnostic accuracy as judged against coronary angiography and scintigraphic perfusion imaging remain yet undefined. The second category of perfusion experiments does not require exogenous contrast agents and has not yet been tested in patient studies. Progress is reported on several MR perfusion-sensitive methods that use the tissue water as an endogenous contrast agent in combination with magnetization transfer techniques as well as paramagnetic deoxyhemoglobin for measuring tissue oxygenation using heavily T2*-weighted sequences for blood oxygen-level-dependent contrast. Possible future directions and developments toward further improvements for MR myocardial perfusion measurements and contraction-perfusion matching are also addressed.

Nikolaos V. Tsekos

Papers

Perfusion imaging by a flow-sensitive alternating inversion recovery (FAIR) technique: application to functional brain imaging.

Magnetic resonance-compatible robotic and mechatronics systems for image-guided interventions and rehabilitation: a review study.

MRI-guided interventional mammary procedures

Design of an MRI-compatible robotic stereotactic device for minimally invasive interventions in the breast.

Concepts of myocardial perfusion imaging in magnetic resonance imaging.