The concept of contrast imaging was introduced to ultrasound almost 30 years ago. The development of ultrasound contrast agents (USCAs), initially slowed by technical limitations, has become more dynamic during the past decade. The ideal USCA should be non-toxic, injectable intravenously, capable of crossing the pulmonary capillary bed after a peripheral injection, and stable enough to achieve enhancement for the duration of the examination. While satisfying cost–benefit requirements, it should provide not only Doppler but also gray-scale enhancement. Already, Doppler examinations are improved by using USCAs when studying deep and small vessels, vessels with low or slow flow, or vessels with a non-optimal insonation angle. Ultrasound contrast agents also enhance detection of flow within abnormal vessels, including tumor vascularization and stenotic vessels, and provide better delineation of ischemic areas. Research is focusing on the development of specific contrast imaging sequences that allow detection of tissue enhancement similar to that obtained with CT or MRI. These sequences take advantage of the non-linear behavior of the microbubbles within the ultrasound field, bringing real-time perfusion imaging for liver, kidney, and the myocardium into reach. New objectives include targeted agents that could further widen USCA applications to specific delivery of active drugs such as anticoagulants or cytotoxic compounds. The combination of new generations of USCAs and new ultrasound image sequences appears to be very promising and currently represents a significant part of ultrasound research.

Ultrasound contrast agents: properties, principles of action, tolerance, and artifacts.

Foreword Part One: History, Basics and Safety of Contrast Agents 1 Contrast Echocardiography - A Historical Perspective PM Shah 2 Principles of Contrast Echo S Meerbaum 3 Conventional Echo Contrast Agents Hand Preparation, Sonication, Properties GP Bezante, D Harpaz, S Reisner, RS Meltzer 4 Albumin Spheres as Contrast Agents JG Wiencek, SB Feinstein 5 Saccharide Based Contrast Agents R Schlief, R Schurmann, T Balzer, M Zomack, H-P Niendorf 6 Echo Contrast Enhancers - How Safe are They? NC Nanda 7 Gas Bubble Dynamics in Acoustic Fields and their Biological Consequences AR Williams, G Kubowicz, R Schlief Part Two: Clinical Uses of Contrast Agents 8 Clinical Use of Contrast Agents - Practical Considerations JR Shapiro, SA Reisner, RS Meltzer 9 Structure Identification by Transthoracic Contrast Echocardiography J Patel, J Cox, A Movahed, W Reeves, NC Nanda 10 Identification of Right Sided Structures by Contrast Transesophageal Echocardiography B Khandheria 11 Left Ventricular Contrast Echocardiography - Echoventriculography R Erbel, R Zotz, S Mohr-Kahaly, N Wittlich, F Schon, R Brennecke, J Meyer 12 Diagnosis of Patent Foramen Ovale by Contrast Transesophageal and Transthoracic Echocardiography D Hausmann, A Mugge, WG Daniel 13 Spontaneous Echographic Contrast - Etiology and Clinical Implications RL Shammas, WC Reeves, NC Nanda 14 Contrast Enhanced Doppler in the Noninvasive Measurement of Pulmonary Artery Pressure NB Schiller 15 Contrast Enhanced Doppler in the Assessment of Aortic Stenosis S Nakatani, KMiyatake 16 Contrast Enhanced Color Doppler - Basics and Potential Clinical Value H Becher, H von Bibra, M Walther, K Glanzer, H Vetter 17 Contrast Enhanced Color Doppler in the Assessment of Mitral Regurgitation H von Bibra, C Firschke, H Becher, H-P Emslander, A Schomig 18 Transesophageal Echo Doppler Studies of Coronary Arteries - Identification, Assessment of Flow Reserve and Value of Contrast Enhancement S Iliceto, C Memmola, V Marangelli, L Carella, P Aragona, C Caiati, P Rizzon 19 Transesophageal Echocardiographic Assessment of Coronary Arteries using Echo Contrast Enhancement EO Ofili, KK Aggarwal, NC Nanda, ColKL Chopra, R Schlief 20 Diagnostic Value of Contrast Enhancement in Vascular Doppler Ultrasound R Schlief, R Schurmann, T Balzer, J Petrick, A Urbank, M Zomack, H-P Niendorf Part Three: Future Perspectives 21 Quantitative Contrast Doppler Intensitometry GP Bezante, KQ Schwartz 22 Role of Echo Contrast in Quantitative Analysis D Rovai, A l'Abbate, AN DeMaria 23 Potential Applications of Color Doppler Imaging of the Myocardium in Assessing Contractility and Perfusion CM Moran, N McDicken, KWE Groundstroem, GR Sutherland 23 Myocardial Imaging by Color Doppler Coded Velocity Mapping - From Regional Contraction to Tissue Characterization? KWE Groundstroem, GR Sutherland, CM Moran, N McDicken Index

Advances in echo imaging using contrast enhancement

Objective: To test the specificity for demyelination of a new neuroimaging sign: contrast enhancement shaped as an open ring or a crescent circumscribed to the white matter. Background: Brain demyelination can cause ring enhancement mimicking neoplasm or infection on CT or MRI. Methods: A MEDLINE search of pathology-proved demyelination yielded 32 illustrated cases of ring-enhancing lesions published between 1981 and 1995. Controls consisted of the same number of published images of neoplasms and infections, pathology proved, and matched by year of publication, and age and gender of the patient. Two neuroradiologists read the images twice independently 1 year apart. Results: Interrater agreement was good (κ = 0.64 and 0.66 for either reading). Test-retest reliability was high (κ = 0.75 and 0.74 for either rater). The open-ring sign clearly distinguished demyelinating lesions from neoplasms and infections. For demyelination versus neoplasm or infection, the specificity of the reading by the first neuroradiologist was 93.8 (95% CI, 86 to 98), and that of the second was 84.4 (95% CI, 74 to 92). The likelihood ratio of demyelination versus neoplasm averaged 5.2, and versus infection, 17.2. That is, if the lesions had the same incidence in the population, in the presence of an open-ring sign demyelination would be five times more likely than neoplasm and 17 times more likely than infection. However, given the much higher incidence of neoplasms and infections, these lesions are still frequently responsible for open-ring enhancement. Conclusions: The open-ring sign is often present in large, contrast-enhancing demyelinating lesions and helps to differentiate them from neoplasms and infections.

Open-ring imaging sign: Highly specific for atypical brain demyelination

The various factors which determine brain weight and volume of the lateral ventricles were studied in an autopsy material of 467 cases. The material consisted of 64 men and 17 women between 45-54 years and 196 men and 190 women between 70-79 years. The weights of the cerebral hemispheres and of the cerebellum and brainstem were determined separately. The volume of the lateral ventricles was determined by weighing the hemispheres with and without water in the lateral ventricles. The recorded variables were age, sex, body length, body weight, cerebral atherosclerosis, Alzheimer changes and alcoholism. Cerebral atherosclerosis and Alzheimer changes were quantitated by morphometric methods. The results were analysed by conventional and multivariate statistical methods. The following observations were made: In normal brains there was a significant correlation between the weight of the supra- and infratentorial parts. Similarly, there was a significant correlation between the size of the lateral ventricles and the weight of the cerebral hemispheres. Women had smaller brains than men even when the difference in body length was taken into account. The difference was approximately 110-115 g for the whole brain after correction for other variables. Women had also smaller lateral ventricles than men, but this difference was in proportion to the smaller size of their hemispheres. There was a physiologic decline in brain weight and a widening of the lateral ventricles with increasing age. This shrinkage probably started after the age of 55. There was a clear correlation between body length and brain weight. The estimated increase in brain weight was approximately 3 g per cm body length. There was a decreasing brain weight and an increasing ventricular size with a decreasing body mass index. This shows that emaciation leads to a decrease in brain size. Severe Alzheimer changes caused a statistically significant enlargement of the lateral ventricles both in men and women. There was a general trend for brain weight reduction in cases with severe Alzheimer changes but the decrease was statistically significant only in old women, and it could not be entirely excluded that the weight reduction in part was due to a concurrent emaciation rather than to the Alzheimer changes per se. In the majority of the cases, the Alzheimer changes were mild and had probably progressed slowly with age. A few cases had very severe changes.(ABSTRACT TRUNCATED AT 400 WORDS)

Ultrasound contrast enhancing agents in neurosonology: principles, methods, future possibilities.

Background Contrast-enhanced ultrasound (CEUS) is a dynamic and continuous modality that offers a real-time, direct view of vascularization patterns and tissue resistance for many organs. Thanks to newer ultrasound contrast agents, CEUS has become a well-established, live-imaging technique in many contexts, but it has never been used extensively for brain imaging. The use of intraoperative CEUS (iCEUS) imaging in neurosurgery is limited. Objective To provide the first dynamic and continuous iCEUS evaluation of a variety of brain lesions. Methods We evaluated 71 patients undergoing iCEUS imaging in an off-label setting while being operated on for different brain lesions; iCEUS imaging was obtained before resecting each lesion, after intravenous injection of ultrasound contrast agent. A semiquantitative, offline interobserver analysis was performed to visualize each brain lesion and to characterize its perfusion features, correlated with histopathology. Results In all cases, the brain lesion was visualized intraoperatively with iCEUS. The afferent and efferent blood vessels were identified, allowing evaluation of the time and features of the arterial and venous phases and facilitating the surgical strategy. iCEUS also proved to be useful in highlighting the lesion compared with standard B-mode imaging and showing its perfusion patterns. No adverse effects were observed. Conclusion Our study is the first large-scale implementation of iCEUS in neurosurgery as a dynamic and continuous real-time imaging tool for brain surgery and provides the first iCEUS characterization of different brain neoplasms. The ability of CEUS to highlight and characterize brain tumor will possibly provide the neurosurgeon with important information anytime during a surgical procedure.

/pdf/intraoperative-contrast-enhanced-ultrasound-for-brain-tumor-4meoudun9a.pdf

Intraoperative contrast-enhanced ultrasound for brain tumor surgery

PURPOSE: To study the potential of contrast material-enhanced transcranial color-coded real-time sonography (TCCS) in detection of primary intracranial tumor vascularization. MATERIALS AND METHODS: Primary central nervous system (CNS) tumors in 28 patients were examined with TCCS before and during administration of a transpulmonary, stable, galactose, microparticle-based ultrasound (US) contrast agent. All patients underwent cranial computed tomography and magnetic resonance imaging; nine patients also underwent intraarterial digital subtraction angiography. RESULTS: All lesions were hyperechoic on B-mode US scans except one grade 2 astrocytoma. The location and extent of hyperechoic lesions correlated well with findings on CT scans and MR images. After injection of contrast material, color Doppler flow signals were seen in nine of 14 low-grade lesions and 14 of 14 high-grade lesions. High-grade malignant tumors always had atypical arterial and venous Doppler spectra with irregular distribution of Doppler...

T Fröhlich

Papers

Vascularization of primary central nervous system tumors: detection with contrast-enhanced transcranial color-coded real-time sonography.

Transcranial duplex sonography using ultrasound contrast enhancers.