Image-guided surgery: From X-rays to Virtual Reality

Since the discovery of X-rays, medical imaging has played a major role in the guidance of surgical procedures. While medical imaging began with simple X-ray plates to indicate the presence of foreign objects within the human body, the advent of the computer has been a major factor in the recent development of this field. Imaging techniques have grown greatly in their sophistication and can now provide the surgeon with high quality three-dimensional images depicting not only the normal anatomy and pathology, but also vascularity and function. One key factor in the advances in Image-Guided Surgery (IGS) is the ability not only to register images derived from the various imaging modalities amongst themselves, but also to register them to the patient. The other crucial aspect of IGS is the ability to track instruments in real time during the procedure, and to portray them as part of a realistic model of the operative volume. Stereoscopic and virtual-reality techniques can usefully enhance the visualization process. IGS nevertheless relies heavily on the assumption that the images acquired prior to surgery, and upon which the surgical guidance is based, accurately represent the morphology of the tissue during the surgical procedure. In many instances this assumption is invalid, and intra-operative real-time imaging, using interventional MRI, Ultrasound, and electrophysiological recordings are often employed to overcome this limitation. Although now in extensive clinical use, IGS is often currently perceived as an intrusion into the operating room. It must evolve towards becoming a routine surgical tool, but this will only happen if natural and intuitive human interfaces are developed for these systems.     

Super-resolution Imaging of Neuronal Dense-core Vesicles

Detection of fluorescence provides the foundation for many widely utilized and rapidly advancing microscopy techniques employed in modern biological and medical applications. Strengths of fluorescence include its sensitivity, specificity, and compatibility with live imaging. Unfortunately, conventional forms of fluorescence microscopy suffer from one major weakness, diffraction-limited resolution in the imaging plane, which hampers studies of structures with dimensions smaller than ~250 nm. Recently, this limitation has been overcome with the introduction of super-resolution fluorescence microscopy techniques, such as photoactivated localization microscopy (PALM). Unlike its conventional counterparts, PALM can produce images with a lateral resolution of tens of nanometers. It is thus now possible to use fluorescence, with its myriad strengths, to elucidate a spectrum of previously inaccessible attributes of cellular structure and organization.Unfortunately, PALM is not trivial to implement, and successful strategies often must be tailored to the type of system under study. In this article, we show how to implement single-color PALM studies of vesicular structures in fixed, cultured neurons. PALM is ideally suited to the study of vesicles, which have dimensions that typically range from ~50-250 nm. Key steps in our approach include labeling neurons with photoconvertible (green to red) chimeras of vesicle cargo, collecting sparsely sampled raw images with a super-resolution microscopy system, and processing the raw images to produce a high-resolution PALM image. We also demonstrate the efficacy of our approach by presenting exceptionally well-resolved images of dense-core vesicles (DCVs) in cultured hippocampal neurons, which refute the hypothesis that extrasynaptic trafficking of DCVs is mediated largely by DCV clusters.     

Semi-automated segmentation and visualisation of outer bone cortex from medical images

Good segmentation of the outer bone cortex from medical images is a prerequisite for applications in the field of finite element analysis, surgical planning environments and personalised, case dependent, bone reconstruction. However, current segmentation procedures are often unsatisfactory. This study presents an automated filter procedure to generate a set of adapted contours from which a surface mesh can be deduced directly. The degree of interaction is user determined. The bone contours are extracted from the patients CT data by quick grey value segmentation. An extended filter procedure then only retains contour information representing the outer cortex as more specific internal loops and shape irregularities are removed, tailoring the image for the above-mentioned applications. The developed medical image based design methodology to convert contour sets of multiple bone types, from tibia tumour to neurocranium, is reported and discussed.     

Magnetic resonance imaging: present and future applications

Magnetic resonance (MR) imaging has created considerable excitement in the medical community, largely because of its great potential to diagnose and characterize many different disease processes. However, it is becoming increasingly evident that, because MR imaging is similar to computed tomography (CT) scanning in identifying structural disorders and because it is more costly and difficult to use, this highly useful technique must be judged against CT before it can become an accepted investigative tool. At present MR imaging has demonstrated diagnostic superiority over CT in a limited number of important, mostly neurologic, disorders and is complementary to CT in the diagnosis of certain other disorders. For most of the remaining organ systems its usefulness is not clear, but the lack of ionizing radiation and MR''s ability to produce images in any tomographic plane may eventually prove to be advantageous. The potential of MR imaging to display in-vivo spectra, multinuclear images and blood-flow data makes it an exciting investigative technique. At present, however, MR imaging units should be installed only in medical centres equipped with the clinical and basic research facilities that are essential to evaluate the ultimate role of this technique in the care of patients.     

Can more K‐selected species be better invaders? A case study of fruit flies in La Réunion

Invasive species are often said to be r -selected. However, invaders must sometimes compete with related resident species. In this case invaders should present combinations of life-history traits that give them higher competitive ability than residents, even at the expense of lower colonization ability. We test this prediction by comparing life-history traits among four fruit fly species, one endemic and three successive invaders, in La Réunion Island. Recent invaders tend to produce fewer, but larger, juveniles, delay the onset but increase the duration of reproduction, survive longer, and senesce more slowly than earlier ones. These traits are associated with higher ranks in a competitive hierarchy established in a previous study. However, the endemic species, now nearly extinct in the island, is inferior to the other three with respect to both competition and colonization traits, violating the trade-off assumption. Our results overall suggest that the key traits for invasion in this system were those that favoured competition rather than colonization.     

Development of a universal interface for the exchange of medical image data using magneto-optical media]

Digital images generated by medical imaging form the basis for radiological diagnosis and surgical planning. Despite the advent of the DICOM 3.0 standard for medical image communication, widespread application of the existing information is often limited by incompatibility of the data formatting used by different equipment generations, and the manufacturer-specific standards employed. An exchange interface based on magneto optical discs has been developed to retrieve and present medical image data regardless of the technological hardware and the specific formats used. Specially adapted routines to retrieve the data first had to be developed. A modular program structure was used to allow flexibility in the implementation of further routines and other exchange media. Over 20,000 CT and MRI images including header information obtained from different General Electric and Siemens scanners were extracted successfully from MO discs. The image data were used for follow up and surgical planning and were transferred to a PAC-server. The interface proved reliable and easy to use. Support for further proprietary formats is currently being developed. The present exchange interface permits reliable retrieval of digital images for diagnostic and surgical planning purposes, regardless of the hardware generation and manufacturer-specific formats.     

High-definition mapping of neural activity using voltage-sensitive dyes

The distribution of patterns of activity in different brain structures has been related to the encoding and processing of sensory information. Consequently, it is important to be able to image the distribution of these patterns to understand basic brain functions. The spatial resolution of voltage-sensitive dye (VSD) methods has recently been enhanced considerably by the use of video imaging techniques. The main factor that now hampers the resolution of VSD patterns is the inherent limitation of the optical systems. Unfortunately, the intrinsic characteristics of VSD images impose important limitations that restrict the use of general deconvolution techniques. To overcomes this problem, in this study an image restoration procedure has been implemented that takes into consideration the limiting characteristics of VSD signals. This technique is based on applying a set of imaging processing steps. First, the signal-to-noise (S/N) ratio of the images was improved to avoid an increase in the noise levels during the deconvolution procedures. For this purpose, a new filter technique was implemented that yielded better results than other methods currently used in optical imaging. Second, focal plane images were deconvolved using a modification of the well-known nearest-neighbor deconvolution algorithm. But to reduce the light exposure of the preparation and simplify image acquisition procedures, adjacent image planes were modeled according to the in-focus image planes and the empirical point spread function (PSF) profiles. Third, resulting focal plane responses were processed to reduce the contribution of optical responses that originate in distant image planes. This method was found to be satisfactory under simulated and real experimental conditions. By comparing the restored and unprocessed images, it was clearly demonstrated that this method can effectively remove the out-of-focus artifacts and produce focal plane images of better quality. Evaluations of the tissue optical properties allowed assessment of the maximum practical optical section thickness using this deconvolution technique in the optical system tested. Determination of the three-dimensional PSF permitted the correct application of deconvolution algorithms and the removal of the contaminating light arising from adjacent as well as distant optical planes. The implementation of this deconvolution approach in salamander olfactory bulb allowed the detailed study of the laminar distribution of voltage-sensitive changes across the bulb layer. It is concluded that (1) this deconvolution procedure is well suited to deconvolved low-contrast images and offers important advantages over other alternatives; (2) this method can be properly used only when the tissue optical properties are first determined; (3) high levels of light scattering in the tissue reduce the optical section capabilities of this technique as well as other deconvolution procedures; and (4) use of the highest numerical aperture in the objectives is advisable because this improves not only the light-collecting efficiency to detect poor-contrast images, but also the spatial frequency differences between adjacent image planes. Under this condition it is possible to overcome some of the limitations imposed by the light scattering/birefringence of the tissue.     

Guide du bon usage de la TDM en médecine nucléaire. IntroductionCT good practices for hybrid nuclear medicine (SPECT/CT and PET/CT): Introduction

Nuclear medicine hybrid imaging is a technological evolution of gamma camera scintigraphy or positron emission tomography imaging methods that are now often coupled with an anatomical imaging device, essentially a CT scanner. Following a large demand from the nuclear physicians themselves, but also from the French Nuclear Safety Authority, this guide is intended for the entire nuclear medicine community to integrate both the aspects of radiation protection related to coupled CT and those related to the quality of the CT images according to the clinical context.     

A simple method for high temporal resolution calcium imaging with dual excitation dyes.

Calcium-sensitive dual excitation dyes, such as fura-2, are now widely used to measure the free calcium concentration ([Ca2+]) in living cells. Preferentially, [Ca2+] is calculated in a ratiometric manner, but if calcium images need to be acquired at high temporal resolution, a potential drawback of ratiometry is that it requires equally fast switching of the excitation light between two wavelengths. To circumvent continuous excitation switching, some investigators have devised methods for calculating [Ca2+] from single-wavelength measurements combined with the acquisition of a single ratiometric pair of fluorescence images at the start of the recording. These methods, however, are based on the assumption that the concentration of the dye does not change during the experiment, a condition that is often not fulfilled. We describe here a method of single-wavelength calcium imaging, in which the dye concentration is estimated from ratiometric fluorescence image pairs acquired at regular intervals during the recording period, that furthermore includes a correction for the changing dye concentration in the calculation of [Ca2+].     

Bilateral synchronous multiple lung nodules: Surgical experience from two cases

Synchronous multiple lung cancer (SMPLC) has been increasingly detected as a result of improved imaging techniques, though the incidence of SMPLC is rare. Surgery is currently the only treatment offering potential cure and long-term survival in patients with SMPLC, and complete resection is widely accepted as the first choice of procedure for this type. However, due to the rarity of this clinical scenario, many surgeons lack experience in surgical treatment of SMPLC. Here, we present two cases whose SMPLC was successfully managed with aggressive surgical therapy through video-assisted thoracoscopic surgery.     

Model-based interpretation of complex and variable images.

The ultimate goal of machine vision is image understanding-the ability not only to recover image structure but also to know what it represents. By definition, this involves the use of models which describe and label the expected structure of the world. Over the past decade, model-based vision has been applied successfully to images of man-made objects. It has proved much more difficult to develop model-based approaches to the interpretation of images of complex and variable structures such as faces or the internal organs of the human body (as visualized in medical images). In such cases it has been problematic even to recover image structure reliably, without a model to organize the often noisy and incomplete image evidence. The key problem is that of variability. To be useful, a model needs to be specific-that is, to be capable of representing only ''legal'' examples of the modelled object(s). It has proved difficult to achieve this whilst allowing for natural variability. Recent developments have overcome this problem; it has been shown that specific patterns of variability in shape and grey-level appearance can be captured by statistical models that can be used directly in image interpretation. The details of the approach are outlined and practical examples from medical image interpretation and face recognition are used to illustrate how previously intractable problems can now be tackled successfully. It is also interesting to ask whether these results provide any possible insights into natural vision; for example, we show that the apparent changes in shape which result from viewing three-dimensional objects from different viewpoints can be modelled quite well in two dimensions; this may lend some support to the ''characteristic views'' model of natural vision.     

Photoacoustic imaging in cancer detection, diagnosis, and treatment guidance

Imaging modalities play an important role in the clinical management of cancer, including screening, diagnosis, treatment planning and therapy monitoring. Owing to increased research efforts during the past two decades, photoacoustic imaging (a non-ionizing, noninvasive technique capable of visualizing optical absorption properties of tissue at reasonable depth, with the spatial resolution of ultrasound) has emerged. Ultrasound-guided photoacoustics is noted for its ability to provide in vivo morphological and functional information about the tumor within the surrounding tissue. With the recent advent of targeted contrast agents, photoacoustics is now also capable of in vivo molecular imaging, thus facilitating further molecular and cellular characterization of cancer. This review examines the role of photoacoustics and photoacoustic-augmented imaging techniques in comprehensive cancer detection, diagnosis and treatment guidance.     

Imaging technologies for the detection of multiple stains in proteomics

Laser-based scanners and charge-coupled device (CCD) camera systems are evolving to have greater functional capabilities for capturing images from a range of staining technologies used in gel electrophoresis and electroblotting. Digitizing Coomassie Brilliant Blue (CBB) stained gels and silver stained gels has now become possible using a laser-based gel scanner, the FLA-5000 fluorescent image analyzer system. Also, a simultaneous dual fluorescent imaging function has been incorporated into the FLA-5000 system, utilizing dichroic mirrors with both the optical system and the emission filter. In the workflow of routine proteomics research, the relationship between SYPRO dye staining and fluorescent detection using the FLA-5000 system have become symbiotic. Additionally in many cases, subsequent staining of the gel with CBB is useful for future research, and thus imaging instruments should be able to handle both staining formats. Digitizing the CBB stained gel can now be easily performed by the FLA-5000 fluorescent image analyzer system using a fluorescent board as an epi-illumination background. A cooled CCD camera system has the potential of imaging not only chemiluminescent membranes but also digitizing molecular weight markers and fluorescent detection of SYPRO dye-stained gels. With Multi Gauge software version 2.0 it is now a simple task to combine two images into one, as commonly required in dual detection experiments. The LAS-3000 system was designed to capture chemiluminescent images and to digitize the images automatically. Thus, new capabilities added to gel imaging systems make them capable of detecting and displaying multiple signals more conveniently.     

When multiphoton microscopy sees near infrared

The need for quantification and real time visualization of developmental processes has called for increasingly sophisticated imaging techniques. Among them, multiphoton microscopy reveals itself to be an extremely versatile tool owing to its unique ability to combine fluorescent imaging, laser ablation, and higher harmonic generation. Furthermore, recent advances in femtosecond lasers and optical parametric oscillators (OPO) are now opening doors for imaging at unprecedented wavelengths centered in the tissue transparency window. This Review describes promising multiphoton approaches using OPO and the growing number of useful applications of non-linear microscopy in the field of developmental biology. Basic characteristics associated with these techniques are described along with the main experimental challenges when applied to embryo imaging.     

Treatment of overactive bladder and incontinence in the elderly

The prevalence of urinary incontinence (UI) and overactive bladder rises with age, and elderly people are the fastest-growing segment of the population. Many elderly people assume UI is a normal part of the aging process and do not report it to their doctors, who must therefore make the effort to elicit the information from them. Coexisting medical problems in older patients and the multiple medications many of them take make diagnosis and treatment more complex in this population. Just as the etiology of incontinence is often multifactorial, the treatment approach may need to be multipronged, with behavioral, environmental, and medical components; in any case, it must be targeted to the individual patient. New, less-invasive surgical techniques and devices make surgery more feasible if other therapy fails.     

Ultrasound-guided Transthoracic Intramyocardial Injection in Mice

Murine models of cardiovascular disease are important for investigating pathophysiological mechanisms and exploring potential regenerative therapies. Experiments involving myocardial injection are currently performed by direct surgical access through a thoracotomy. While convenient when performed at the time of another experimental manipulation such as coronary artery ligation, the need for an invasive procedure for intramyocardial delivery limits potential experimental designs. With ever improving ultrasound resolution and advanced noninvasive imaging modalities, it is now feasible to routinely perform ultrasound-guided, percutaneous intramyocardial injection. This modality efficiently and reliably delivers agents to a targeted region of myocardium. Advantages of this technique include the avoidance of surgical morbidity, the facility to target regions of myocardium selectively under ultrasound guidance, and the opportunity to deliver injectate to the myocardium at multiple, predetermined time intervals. With practiced technique, complications from intramyocardial injection are rare, and mice quickly return to normal activity on recovery from anesthetic. Following the steps outlined in this protocol, the operator with basic echocardiography experience can quickly become competent in this versatile, minimally invasive technique.     

The Wellcome Foundation lecture, 1981. Nuclear magnetic resonance imaging in medicine: physical principles

In recent years nuclear magnetic resonance (n.m.r.) has become a means of providing excellent images of the interior of the human body which are proving useful in medical practice. The development of n.m.r. imaging, much of which was pioneered in Britain, is outlined. Proton image resolution of human anatomy is comparable with X-ray computed tomography images, but without the hazard of ionizing radiation. There is improved soft tissue discrimination and pathological contrast through the basic imaging parameters of the proton density and the relaxation times T1 and T2, whose differences from one tissue to another are exploited by use of appropriate radiofrequency pulse sequences. Images may be obtained directly of transverse, coronal and sagittal sections of the head and body. Single slices or multiple slices may be imaged and imaging may be done in three dimensions. The lecture describes the more important imaging techniques and gives illustrative examples of images obtained. The efficient use of time in n.m.r. imaging is discussed, particularly mentioning the multiecho-multislice procedure and the development of real-time n.m.r. imaging. Magnetic field strengths in current use for proton n.m.r. imaging range from 0.02 to 2 T. At the lower end of the range resistive magnets are used, while for higher fields superconducting magnets are needed. A considerable improvement in image quality is obtained by use of special receiver coils.     

Reduction of image artifacts in mice by bladder flushing with a novel double-lumen urethral catheter

In electron paramagnetic resonance imaging (EPRI), the accumulation of contrast agent in the bladder can create a very large source of signal, often far greater than that of the organ of interest. Mouse model images have become increasingly important in preclinical testing. To minimize bladder accumulation on mouse images, we developed a novel, minimally invasive, MRI/EPRI-friendly procedure for flushing a female mouse bladder. It is also applicable to other imaging techniques, for example, PET, SPECT, etc., where contrast agent accumulation in the bladder is also undesirable. A double-lumen urethral catheter was developed, using a standard IV catheter with a silicone tube extension, having a polyethylene tube threaded into the IV catheter. Flushing of the bladder provides a substantial reduction in artifacts, as shown in images of tumors in mice.     

Brain Magnetic Resonance in the Diagnostic Evaluation of Mitochondrial Encephalopathies

Brain MR imaging techniques are important ancillary tests in the diagnosis of a suspected mitochondrial encephalopathy since they provide details on brain structural and metabolic abnormalities. This is particularly true in children where non-specific neurologic symptoms are common, biochemical findings can be marginal and genetic defects may be not discovered. MR imaging modalities include conventional, or structural, imaging (MRI) and functional, or ultrastructural, imaging (spectroscopy, MRS; diffusion, DWI-ADC; perfusion, DSCI––ASL). Among them MRI and MRS are the main tools for diagnosis and work up of MD, and this review will focus mainly on them. The MRI findings of MD are very heterogeneous, as they depend on the metabolic brain defects, age of the patient, stage and severity of the disease. No correlation has been found between genetic defects and neuroimaging picture; however, some relationships between MR findings and clinical phenotypes may be identified. Different combinations of MRI signal abnormalities are often encountered but the most common findings may be summarized into three main MR patterns: (i) non-specific; (ii) specific; (iii) leukodystrophic-like. Regarding the functional MR techniques, only proton MRS plays an important role in demonstrating an oxidative metabolism impairment in the brain since it can show the accumulation of lactate, present as a doublet peak at 1.33 ppm. Assessment of lactate should be always performed on brain tissue and on the ventricular cerebral spinal fluid. As for MRI, metabolic MRS abnormalities can be of different types, and two distinct patterns can be recognized: non-specific and specific. The specific metabolic profiles, although not frequent to find, are highly pathognomonic of MD. The un-specific metabolic profiles add value to structural images in allowing to define the lesion load and to monitor the response to therapy trials.     

Spectroscopic imaging at compact inverse Compton X-ray sources

While K-edge subtraction (KES) imaging is a commonly applied technique at synchrotron sources, the application of this imaging method in clinical imaging is limited although results have shown its superiority to conventional clinical subtraction imaging. Over the past decades, compact synchrotron X-ray sources, based on inverse Compton scattering, have been developed to fill the gap between conventional X-ray tubes and synchrotron facilities. These so called inverse Compton sources (ICSs) provide a tunable, quasi-monochromatic X-ray beam in a laboratory setting with reduced spatial and financial requirements. This allows for the transfer of imaging techniques that have been limited to synchrotrons until now, like KES imaging, into a laboratory environment. This review article presents the first studies that have successfully performed KES at ICSs. These have shown that KES provides improved image quality in comparison to conventional X-ray imaging. The results indicate that medical imaging could benefit from monochromatic imaging and KES techniques. Currently, the clinical application of KES is limited by the low K-edge energy of available iodine contrast agents. However, several ICSs are under development or already in commissioning which will provide monochromatic X-ray beams with higher X-ray energies and will enable KES using high-Z elements as contrast media. With these developments, KES at an ICS has the ability to become an important tool in pre-clinical research and potentially advancing existing clinical imaging techniques.