ICUS Weekly News Monitor 10-31-2008

1. MarketWatch, Oct 27, 2008 Cardiovascular Diagnostic Center Limits Radiation and Contrast Dosage Using Toshiba's Industry Leading Technology 2. News-Medical.Net (Sydney, Australia), Oct 26, 2008 Sensitive ultrasound to spot early-stage cancer 
 MarketWatch Oct 27, 2008 Cardiovascular Diagnostic Center Limits Radiation and Contrast Dosage Using Toshiba's Industry Leading Technology The diagnosis and subsequent treatment of cardiovascular disease can be accomplished through a variety of medical imaging modalities. Demonstrating the effectiveness of a multi-modality approach, Salinas Valley Memorial Healthcare System created the Cardiovascular Diagnostic Center at its Ryan Ranch outpatient facility in Monterey County, Calif. to provide cardiac disease treatment to its patients with a full suite of imaging equipment from Toshiba America Medical Systems, Inc. Salinas Valley Memorial Healthcare System will use the Toshiba Aquilion(R) ONE computed tomography (CT) system and the Vantage(TM) Atlas magnetic resonance (MR) system to deliver the highest quality of patient care. In addition, Toshiba's Aplio(TM) Artida ultrasound system is being used by Salinas Valley's director at his professional practice to further evaluate cardiac patients. The Cardiovascular Diagnostic Center is led by Dr. Timothy Albert, assistant consulting professor of medicine at Duke University. The Cardiovascular Diagnostic Center is the only facility in California to use these Toshiba technologies side-by-side to provide imaging with low doses of contrast and radiation. "Using a combination of the latest CT, MR and ultrasound technologies allows us to offer the most effective and safest patient care to the community," said Dr. Albert, director, Cardiovascular Diagnostic Center, Salinas Valley Memorial Healthcare System. "When a patient is displaying a specific set of symptoms, we are capable of imaging them right away on the most appropriate system. That way, we can reduce both the contrast and radiation dose a patient receives." The Cardiovascular Diagnostic Center acquired the Toshiba Aquilion ONE dynamic volume CT system to perform advanced cardiovascular CT imaging. The Aquilion ONE utilizes 320 ultra-high resolution detector rows (0.5 mm in width) to image the heart in a single gantry rotation. The result is unparalleled in diagnostic imaging today and produces a 4D clinical video showing up to 16 cm of anatomical coverage, enough to capture the entire heart, and show its movement such as blood flow. "CT is the gold standard for coronary imaging because of the high image resolution and fast acquisition time," stated Dr. Albert. "The rapid, efficient cardiac imaging and the lower radiation dose of the Aquilion ONE CT system was a perfect fit for the new cardiovascular center. The Aquilion ONE is able to lower radiation dosage by up to 80 percent, making CT imaging safer for patients." The Center will use Toshiba's Vantage Atlas MR system in the diagnosis of cardiovascular disease and Toshiba's proprietary contrast-free MR methods to improve patient safety. Unlike some other diagnostic tests, MR shows both anatomy and function, such as blood flow, and is used in analyzing valve structure and heart function. Additionally, MR offers an imaging alternative without any radiation. "MR has revolutionized the way we look at the heart," explained Dr. Albert. "New MR technology creates movie-quality images of the heart, which is like the difference between old black and white television versus today's high-definition television." The Center will also take advantage of Toshiba's industry leading, proprietary contrast-free MR techniques, which include Fresh Blood Imaging (FBI), Contrast-free Improved Angiography (CIA), Time-Spatial Labeling Inversion Pulse (Time-SLIP) and Time and Space Angiography (TSA). The contrast-free protocols are particularly important in imaging vascular disease and patients with kidney dysfunction. At Dr. Albert's professional practice, he uses the Toshiba Aplio Artida ultrasound in the evaluation of heart muscle and valve function. The 4D imaging and 3D wall motion tracking create detailed images allowing for the highest levels of diagnostic confidence. "The work being done by Dr. Albert and Salinas Valley Memorial Healthcare System will change the way physicians use the full suite of Toshiba systems, including CT, MR and ultrasound to diagnose cardiovascular disease," said Girish Hagan, vice president, Marketing, Toshiba. "Across the board, Toshiba's advanced technology is making medical imaging safer for patients by dramatically reducing radiation and eliminating contrast agents in certain procedures." About Salinas Valley Memorial Healthcare System Salinas Valley Memorial Hospital is a Public District Hospital that is part of the Salinas Valley Memorial Healthcare System. The Healthcare System is an integrated network of health care programs, services and facilities. At the core of the system is a 269-bed acute care hospital with several distinct specializations and programs, including the Regional Heart Program, the Comprehensive Cancer Center, a Level III Neonatal Intensive Care Unit (NICU), Joint Replacement Center, and the Regional Spine Center. Salinas Valley Memorial employs more than 2,200 people and the Medical Staff includes 265 board-certified physicians across a range of specialties. News-Medical.Net (Sydney, Australia) Oct 26, 2008 Sensitive ultrasound to spot early-stage cancer European researchers have developed highly sensitive ultrasound equipment that can detect tiny quantities of reflective microbubbles engineered to stick to specific tumour cells. The technique should pick up tumours early and improve patients' chances of survival. Most of the current diagnostic methods - biopsy analysis, biochemical tests and medical imaging - are not sufficiently sensitive. They frequently return a false negative; the tumour is only discovered when it is much bigger, and too late. European researchers are developing a new technique that will help medical professionals visualise tiny quantities of pathological tissue in patients. The technology could localise tumours in their very earliest stages of development and help doctors begin treatments much earlier, giving patients a much better chance of survival. The new approach uses medical ultrasound, a safe technology most commonly used for pre-natal visualisation of the foetus and the imaging of other soft tissues. A probe sends high-frequency acoustic waves into the body and detects how they bounce off the interfaces between different tissues. To improve the sensitivity of this imaging technique, a sonographer may sometimes inject a so-called contrast agent into patients, which greatly increases the scattering of the acoustic waves back to the probe. For ultrasound imaging, contrast agents are based on 'microbubbles', micron-sized gas-filled balls that show up brightly on the ultrasound image. Researchers in the EU-funded TAMIRUT project have developed a microbubble medium that can specifically target and bind to certain pathogenic cells in the body (such as endothelial cells of vessels lining the tumours). Combined with enhanced ultrasound equipment and signal processing capabilities, the system can detect where microbubbles adhere to target cells, and reveal the presence of early-stage tumours. Working with the pharmaceutical company Bracco Research S.A. in Switzerland, TAMIRUT researchers have developed a way to attach antibodies onto the surface of microbubbles. By selecting an antibody with an affinity for marker molecules found only on target vascular cells, the microbubbles 'stick' only to the target cells. But it is not easy to pick up these hotspots on a scan. "We are looking at the very earliest stages of tumour growth, so there are not many cells present expressing the marker of interest," explains Alessandro Nencioni who coordinated the project. "There may be only three or four microbubbles adhered to a site and current ultrasound equipment is not able to pick these up. Work on the hardware and signal processing is an essential aspect of this project as we seek to develop next-generation ultrasound imaging capabilities." Strong signals Esaote, an Italian manufacturer of medical imaging equipment, is working with several research partners and two SMEs: Vermon, a French manufacturer of medical imaging probes, and SignalGeneriX, a small firm based in Cyprus with expertise in signal processing. Their aim is to produce a scanner and a dedicated probe that can transmit and receive ultrasound waves across a wide range of frequencies and wave forms in order to exploit (without any modification) the harmonic components caused by nonlinear scattering of the acoustic wave of the microbubbles. The scanning equipment must have sufficient processing power to interpret the waves picked up by the probe, update the live image and adjust the transmitted waveforms in real time. Their detecting function is ensured by a specifically developed signal processing methods, able to detect a very limited number of microbubbles (down to a single bubble), to estimate their concentration, and to track their behaviour to get the diagnostic answer searched. Originally, the project partners thought it would be possible to differentiate between bound and unbound microbubbles by the way they scatter particular ultrasound frequencies and wave forms. However, extensive simulations and laboratory testing have shown that this turns out to be very difficult. Instead, the scientists found a very simple answer: after 10 minutes, the microbubbles that are attached to target cells remain in place while the free microbubbles diffuse away. The new probe will detect and calculate their local concentration and operators will be able to visualise any areas of high microbubble density within an entire organ. The repetition of this new imaging technique over time could help medical staff to assess the evolution of a tumour, especially its vascularisation. Using the engineered, targeted microbubble contrast agent, the improved ultrasound hardware and the signal processing, the TAMIRUT team has already demonstrated in simulations the potential of this approach for the early detection of prostate cancer. "Our approach goes a long way to eliminating or strongly reducing the problem of false-negative diagnosis," says Nencioni, "offering a second degree of evaluation after blood test screening. It is sensitive, specific and you are able to examine the whole organ, which is not possible by biopsy." This ultrasound method improves accuracy, patient comfort and costs around half that of a biopsy. It could save European healthcare providers up to ?250 million each year in biopsy costs alone. The need for clinical trials of the targeted contrast agent and subsequent approval in humans means that the targeted microbubble agent is unlikely to be available for at least three years. But the improved signal processing algorithms will help to increase the sensitivity of ultrasound equipment, irrespective of the use of these microbubbles. Esaote is working with the other commercial partners to incorporate the new signal processing features into its medical imaging equipment by the end of 2009.

ICUS Weekly News Monitor 10-24-2008

1. The Earth Times, Oct 23, 2008 Hospitals, Healthcare Providers to Save with Premier Agreement for Cardiac Ultrasound Contrast Media 2. PhysOrg.com, Oct 23, 2008 Sensitive ultrasound to spot early-stage cancer 3. Orthopedics, Oct 2008 External Fixation and Pseudoaneurysm: Report of a Case Related to Tibial Lengthening By Athanassios Papanikolaou, MD; Christos Thanassas, MD; George Arealis, MD; John Maris, MD 
 The Earth Times Oct 23, 2008 Hospitals, Healthcare Providers to Save with Premier Agreement for Cardiac Ultrasound Contrast Media Charlotte, NC -- Premier Purchasing Partners, LP, today announced a new agreement for cardiac ultrasound contrast media with Lantheus Medical Imaging of North Billerica, Mass. The new agreement includes the Definity® cardiac ultrasound agent formerly available through Bristol-Myers Squibb. In January 2008, Bristol-Myers Squibb sold its medical imaging division to Avista Capital Partners; the new company was named Lantheus Medical Imaging. Effective December 1, 2008, the 36-month agreement is available to acute and continuum of care members of the Premier healthcare alliance. PhysOrg.com Oct 23, 2008 Sensitive ultrasound to spot early-stage cancer European researchers have developed highly sensitive ultrasound equipment that can detect tiny quantities of reflective microbubbles engineered to stick to specific tumour cells. The technique should pick up tumours early and improve patients' chances of survival. Most of the current diagnostic methods – biopsy analysis, biochemical tests and medical imaging – are not sufficiently sensitive. They frequently return a false negative; the tumour is only discovered when it is much bigger, and too late. 

European researchers are developing a new technique that will help medical professionals visualise tiny quantities of pathological tissue in patients. The technology could localise tumours in their very earliest stages of development and help doctors begin treatments much earlier, giving patients a much better chance of survival. 

The new approach uses medical ultrasound, a safe technology most commonly used for pre-natal visualisation of the foetus and the imaging of other soft tissues. A probe sends high-frequency acoustic waves into the body and detects how they bounce off the interfaces between different tissues. 

To improve the sensitivity of this imaging technique, a sonographer may sometimes inject a so-called contrast agent into patients, which greatly increases the scattering of the acoustic waves back to the probe. For ultrasound imaging, contrast agents are based on ‘microbubbles’, micron-sized gas-filled balls that show up brightly on the ultrasound image. 

Researchers in the EU-funded TAMIRUT project have developed a microbubble medium that can specifically target and bind to certain pathogenic cells in the body (such as endothelial cells of vessels lining the tumours). Combined with enhanced ultrasound equipment and signal processing capabilities, the system can detect where microbubbles adhere to target cells, and reveal the presence of early-stage tumours. 

Working with the pharmaceutical company Bracco Research S.A. in Switzerland, TAMIRUT researchers have developed a way to attach antibodies onto the surface of microbubbles. By selecting an antibody with an affinity for marker molecules found only on target vascular cells, the microbubbles ‘stick’ only to the target cells. 

But it is not easy to pick up these hotspots on a scan. “We are looking at the very earliest stages of tumour growth, so there are not many cells present expressing the marker of interest,” explains Alessandro Nencioni who coordinated the project. 

“There may be only three or four microbubbles adhered to a site and current ultrasound equipment is not able to pick these up. Work on the hardware and signal processing is an essential aspect of this project as we seek to develop next-generation ultrasound imaging capabilities.” 

Strong signals 

Esaote, an Italian manufacturer of medical imaging equipment, is working with several research partners and two SMEs: Vermon, a French manufacturer of medical imaging probes, and SignalGeneriX, a small firm based in Cyprus with expertise in signal processing. Their aim is to produce a scanner and a dedicated probe that can transmit and receive ultrasound waves across a wide range of frequencies and wave forms in order to exploit (without any modification) the harmonic components caused by nonlinear scattering of the acoustic wave of the microbubbles. 

The scanning equipment must have sufficient processing power to interpret the waves picked up by the probe, update the live image and adjust the transmitted waveforms in real time. Their detecting function is ensured by a specifically developed signal processing methods, able to detect a very limited number of microbubbles (down to a single bubble), to estimate their concentration, and to track their behaviour to get the diagnostic answer searched. 

Originally, the project partners thought it would be possible to differentiate between bound and unbound microbubbles by the way they scatter particular ultrasound frequencies and wave forms. However, extensive simulations and laboratory testing have shown that this turns out to be very difficult. Instead, the scientists found a very simple answer: after 10 minutes, the microbubbles that are attached to target cells remain in place while the free microbubbles diffuse away. 

The new probe will detect and calculate their local concentration and operators will be able to visualise any areas of high microbubble density within an entire organ. The repetition of this new imaging technique over time could help medical staff to assess the evolution of a tumour, especially its vascularisation. 

Using the engineered, targeted microbubble contrast agent, the improved ultrasound hardware and the signal processing, the TAMIRUT team has already demonstrated in simulations the potential of this approach for the early detection of prostate cancer. 

“Our approach goes a long way to eliminating or strongly reducing the problem of false-negative diagnosis,” says Nencioni, “offering a second degree of evaluation after blood test screening. It is sensitive, specific and you are able to examine the whole organ, which is not possible by biopsy.” 

This ultrasound method improves accuracy, patient comfort and costs around half that of a biopsy. It could save European healthcare providers up to €250 million each year in biopsy costs alone. 

The need for clinical trials of the targeted contrast agent and subsequent approval in humans means that the targeted microbubble agent is unlikely to be available for at least three years. But the improved signal processing algorithms will help to increase the sensitivity of ultrasound equipment, irrespective of the use of these microbubbles. 

Esaote is working with the other commercial partners to incorporate the new signal processing features into its medical imaging equipment by the end of 2009. 

TAMIRUT project received funding from the ICT strand of the Sixth Framework Programme for research Orthopedics Oct 2008 External Fixation and Pseudoaneurysm: Report of a Case Related to Tibial Lengthening By Athanassios Papanikolaou, MD; Christos Thanassas, MD; George Arealis, MD; John Maris, MD
 External fixators provide a mechanically stable environment to allow fracture stabilization or limb lengthening. Most complications are related to pin or wire insertion. This article presents the case of a 33-year-old man who sustained an open fracture of his left tibia with consequent infection and bone loss. The procedure of tibial lengthening was complicated by late formation of a pseudoaneurysm of the distal popliteal artery after exchange of the proximal pins of the fixator. Case Report A 33-year-old male drug addict was admitted to our hospital after a motorcycle accident. He had sustained an open fracture of the lower third of his left tibia, Gustillo type IIIB. The initial treatment was debridement and stabilization with a Hoffmann II external fixator (Stryker, Mahwah, New Jersey). Seven days later the wound was covered with a skin graft. One month later the patient developed fever, inflammation, and pyorrhea due to osteomyelitis. Resection of the infected peripheral segment of the tibia and ankle fusion were performed using an Orthofix monolateral external fixation (LRS; Orthofix, McKinney, Texas). After 2 months a proximal tibial osteotomy was performed and lengthening of the shortened tibia was begun with the assistance of a monolateral external fixator (LRS; Orthofix). Eight centimeters of lengthening were achieved with angulation and poor callus formation. Therefore, 10 months after the osteotomy the malunion was corrected and the position of the proximal pins, which were loose, was changed; they were placed more posteriorly in order to achieve a better grip. At the same time autologous and heterologous bone graft was applied. Six weeks postoperatively, a large mass at the posterior tibial compartment was noticed. The mass was not pulsating. The posterior tibial artery was palpable, but the pulse of the dorsalis pedis artery was absent. The hematocrit was low (25%). An ultrasound and computed tomography (CT) scan were performed. They showed a cystic mass in the calf with a diameter of 6 cm. Enhancement after administration of contrast material in the CT scan suggested an aneurysm (Figure 1). A digital subtraction angiography confirmed the existence of a false aneurysm of the distal popliteal artery (Figure 2). The anterior tibial artery was missing. Transarterial vascular repair using a stent was successfully performed. However, the patient developed a persistent infection at the site of the callus and a below-knee amputation was ultimately performed. Discussion False aneurysm is a rare vascular complication resulting from the use of external fixators. Other complications include acute ischemia, bleeding, compartment syndrome, and arteriovenous fistula. The first theory to explain the etiology of false aneurysms in relation to external fixation was direct vascular damage from the inappropriate position of pins or wires that gives clinical symptoms within days or weeks.1 It is remarkable that pseudoaneurysms are reported following pin or wire withdrawal as well.2 In order to explain this, as well as the late appearance of some lesions, the theory of vascular lesion due to erosion from contact with a pin or a wire has been introduced.3 This is supported by a study by Dwyer,4 who found that it is almost impossible to pierce any major vessel with the pins. Another cause of pseudoaneurysm formation that has been reported is bone distraction.5 Lengthening may either aggravate an unrecognized surgical arterial injury or precipitate de novo rupture of an artery scarred from a previous trauma. Similarly, corticotomy in combination with the distraction process has been held responsible for a case of a peroneal artery aneurysm with arteriovenous fistula.6 In the present case the pseudoaneurysm was noticed 6 weeks after the application of the monolateral lengthening fixator. The site of the arterial injury was at the level of the most distal of the 3 proximal pins. Since the lengthening procedure had come to an end, direct injury of the artery when the pins were exchanged is the most plausible explanation. Infection that was not evident at that time may have also have played a role. The missing anterior tibial artery was probably due to thrombosis caused by previous injuries. Another explanation could be that the aneurysm originated from the bifurcation of the popliteal artery, thus occluding the anterior tibial artery. However, in the latter case one might observe the distal part of the artery filled by the collaterals. We were able to find only 7 cases in the literature of arterial pseudoaneurysm related to application of external fixation to the tibia: 2 cases affecting the peroneal artery,2,6 3 affecting the anterior tibial artery,5,7,8 1 affecting the distal popliteal artery,3 and 1 affecting the deep femoral artery.9 The popliteal artery is more commonly injured when fixators are placed at the femur. Four cases were related to limb lengthening and 3 to fractures. Ilizarov external fixation was used in 5 cases. Clinical symptoms are presented early if there is an immediate arterial injury or late if the lesion is due to erosion from impingement.6 The symptoms are bleeding through the pin holes, lowering of hematocrit level, appearance of a mass (often pulsating), and sometimes pain. Possible complications from a false aneurysm are bleeding, occlusion and ischemia, rupture and compartment syndrome, and infection from contamination by an infected pin. The treatment of a false aneurysm depends on the site, size, aneurysmal neck, and experience of the surgeon.10 If it is small (<10 mm) and involves an artery of minor importance, it can be simply observed. Larger aneurysms, those that become symptomatic (pain, bleeding, ischemia, infection), or those that involve major arteries in which occlusion would threaten severe ischemic effects, require intervention.3 Treatment can be open repair using venous or artificial graft, endovascular repair by stents, ultrasound-guided compression, or percutaneous thrombin injection. Conclusion The formation of a false aneurysm of the popliteal artery or its branches after application of an external fixation is a rare complication that usually becomes symptomatic days to months after the injury as the aneurysm grows. High suspicion index is necessary for the diagnosis, since mere local swelling may be the only sign. Triplex sonography or angiography is necessary for confirmation. Endovascular treatment can be an effective, minimally invasive management for this serious complication.

ICUS Weekly News Monitor 10-17-2008

1. DOTmed News, Oct 17, 2008, Philips Combines Ultrasound With Cancer Drug Delivery By Lynn Shapiro 2. Science Centric, Oct 16. 2008 Why contrast-enhanced ultrasound better than intraoperative ultrasound ? 3. The Engineer, Oct 15, 2008, Targeted delivery By Siobhan Wagner 4. 7thSpace Interactive, Oct 13, 2008, The usefulness of contrast during exerciseechocardiography for the assessment of systolic pulmonary pressure By Luis R Lopes & et al 5. AuntMinnie.com, Oct 13, 2008, Acusphere's Imagify to get FDA review DOTmed News Oct 17, 2008 Philips Combines Ultrasound With Cancer Drug Delivery By Lynn Shapiro, Writer In its first foray into the pharmaceutical arena, Philips is combining its ultrasound bubble system, now used for the diagnosis of heart failure and liver disease, with a drug delivery system for cancer drugs. "We have found a way to load drugs inside these bubbles while using the contrast agents as well," Steve King, communications manager for research tells DOTmed News. 

"We inject the drug-filled microbubbles in the patient's bloodstream and follow the bubbles with ultrasound imaging. When we see the bubbles reach the tumor, we use a higher energy focused ultrasound wave to burst the bubbles and release the drugs into the tumor." 

Philips is betting that this localized drug delivery system will reduce the side effects of chemotherapy without compromising its efficacy. 

So far, Philips researchers have tested the cancer drug, paciltaxel, in mice. King says while local drug delivery is feasible, Philips is only in the first stage of developing its new chemo technology. He believes it will be five years before clinical studies on human beings can begin. "Philips is not into cancer medicine and cannot enter this field alone," King says. The company is now attempting to find a pharmaceutical partner to help develop research studies. 

"Pre-clinical experiments make us very confident that this system will work," King says. The company is now working with the University of Virginia, where researchers did their preclinical studies. 

Full caption: 
The microbubbles are tiny gas-filled spheres of biodegradable material no bigger than red blood cells. These are to be injected into the patient's bloodstream and carried to the site of a tumor. The arrival of the microbubbles at the tumor can be monitored with ultrasound imaging. Science Centric Oct 16. 2008 Why contrast-enhanced ultrasound better than intraoperative ultrasound ? IOUS is an important tool in the fields of surgery for liver tumours, but it also has some drawbacks such as lacking of specificity to differentiate cirrhotic nodules from small malignant nodules. Contrast-enhanced ultrasound was shown with improved nodule characterisation by recent studies. The research team led by Prof. Yan Luo from West China Hospital found that besides the merits of IOUS, CE-IOUS shows tumour vascularity and tissue microcirculation by applying intravenous ultrasound contrast agents, thus helps to differentiate malignant nodules from benign ones. Therefore it helps surgeons to eradicate malignant nodules and avoid unnecessary intervention of benign ones. Their finding were published on 7 July 2008 in the World Journal of Gastroenterology. Due to the high sensitivity and specificity of CE-IOUS to find malignant liver tumours, this new technique should be used more frequently in surgeries for cirrhotic livers. Although this study includes only a short number of patients, the research is quite interesting and the results are relevant to improve the quality of hepatic surgery. The Engineer Oct 15, 2008 Targeted delivery By Siobhan Wagner A new minimally invasive procedure that attacks cancerous cells only at the site of diseased tissue is claimed to cause patients fewer ill effects.

The treatment, which is being studied by researchers at Philips Research and various academic institutions, involves injecting patients with microscopic polymer bubbles filled with anti-cancer drugs. The bubbles are then tracked in the bloodstream with ultrasound imaging and burst using a focused ultrasound pulse to release the drugs at the desired spot.

'Traditional chemotherapy is administered to every part of the body and is certainly an effective therapy for patients, but it does have side effects,' said Steve Klink, a spokesman for Philips. 'One way to reduce these is to reduce the dose,' he added.

But he added that while this may cut down on the side effects, it will also reduce the effectiveness.

Klink explained that with the new method the drugs are only administered to the region where they are needed. 'Of course, the microbubbles also reach other regions of the body as they travel through the bloodstream, but since the drugs are encapsulated in a microbubble patients will not feel any side effects.' he said.

Philips is working with several academic partners, including the University of Virginia in the US, where pre-clinical experiments are being performed on mice, and the University of Münster in Germany to refine the technology. Clinical trials, said Klink, are no nearer than five years away.

This is not the first use of microbubbles with medical ultrasound imaging. In current clinical practice, doctors use gas-filled microbubbles as contrast agents. Microbubbles can be used, for example, to highlight blood in ultrasound images because they reflect ultrasound waves better than blood or soft tissue.

This latest drug delivery technology being developed at Philips continues to use the contrast-enhancing capabilities of microbubbles so that ultrasound operators can locate tumours, which appear as dense masses surrounded by a network of small blood vessels.

The new part of the technology involves shattering the microbubble shells in the blood vessels using a focused high-energy ultrasound pulse. As a result of this, the drugs in the microbubbles are released directly inside the tumour.

Klink said the microbubbles are typically less than five microns across, which is about the size of a red blood cell, and their shell is made of polylactic acid - a biodegradable, thermoplastic polyester derived from renewable sources such as corn starch.

'We have developed a way to incorporate a liquid that contains the anti-cancer drug inside the microbubble,' he said, adding that the bubbles are only partly filled. 'We want to maintain air in them so the bubbles still retain their contrast agent capabilities. The air also allows the bubbles to burst easier.'

The bubbles are created by mixing a solution consisting of a carrier solvent, an oil that can be removed after freeze-drying, another oil with an anti-cancer drug dissolved in it and a polymer.

Inkjet droplets of this solution are dropped into water where they form into polymer capsules. The capsules are then freeze-dried, which results in polymer microbubbles filled with anti-cancer drugs and air.

Klink said the other innovation involved in the research is a computer-controlled ultrasound device that can steer and focus the microbubble-rupturing ultrasound pulses.

Philips researchers developed a special phased-array transducer that can focus ultrasound pulses into a small ellipsoidal volume up to 10cm deep in the target tissue.

In the experimental prototype developed by Philips, the phased array transducer is co-aligned with a standard clinical imaging transducer so that the ultrasound imaging and drug delivery could be performed simultaneously.

The researchers believe they may be able to make use of the way microbubbles generate their own acoustic signal when they burst. This information could help doctors tell how many microbubbles have ruptured, which could allow them to quantify and control drug dosage.

Beyond this drug delivery application, Philips researchers believe their transducer might also be optimised to produce other bio-effects such as thrombolysis (clot busting). The microbubble payload delivery system could also have applications in gene therapy.

 7thSpace Interactive Oct 13, 2008 The usefulness of contrast during exerciseechocardiography for the assessment of systolic pulmonary pressure By Luis R Lopes, Maria J Loureiro, Rita Miranda, Sofia Almeida, Ana R Almeida, Ana Cordeiro, Carlos Cotrim and Manuel Carrageta
 The systolic pulmonary artery pressure (PAPs) can be accurately estimated, non-invasively, using continuous-wave Doppler (CWD) ultrasound measurement of the peak velocity of a tricuspid regurgitant (TR) jet.However, it is often difficult to obtain adequate tricuspid regurgitation signals for measurement of PAPs, what could lead to its underestimation. Therefore, utilization of air-blood-saline contrast has been implemented for the improvement of Doppler signal in several clinical contexts.

It is now recommended in the evaluation of patients with pulmonary hypertension. Physical activity is severely restricted in patients with PAH, being exertional dypnea the most typical symptom.

Exercise stress echo-Doppler imaging allows assessment of the response to exercise. It is an excellent screening test for patients with suspected PAH.

Our purpose was to evaluate the value and accuracy of agitated saline with blood contrast echocardiography, in the improvement of the Doppler signal, to quantify PAPs during treadmill exercise-echocardiography.Purpose: To evaluate the value of contrast echocardiography, using agitated saline with blood, in the improvement of the Doppler signal used to quantify the pulmonary artery systolic pressure during exercise. 

Methods: From a total of 41 patients (pts), we studied 38 pts (93%), 35 women, aged 54 +/- 12 years-old.

27 with the diagnosis of systemic sclerosis, 10 with history of pulmonary embolism and one patient with a suspected idiopathic PAH, who were referred to the Unity of Heart Failure and Pulmonary Hypertension for screening of PAH. According to the Unity protocol, a transthoracic echocardiogram was made, in left decubitus (LD), with evaluation of right ventricle-right atria gradient (RV/RAg).

A peripheral venous access was obtained, with a 3-way stopcock and the patients were placed in orthostatism (O), with a new evaluation of RV/RAg. Exercise echocardiography (EE) was begun, with evaluation of RV/RAg at peak exercise (P) and afterwards agitated saline (8cc with 1cc of air and 1cc of blood) was injected, followed by a new evaluation of RV/RAg (PC) and then the interruption of the EE.

Pulmonary Hypertension was diagnosed when RV/RAg at the end of the exercise was superior to 40 mmHg. 

Results: The quality of Doppler signal was deteriorated in 5 pts, maintained in 6 pts and improved in 26 pts, with the use of contrast.

In one patient, an interventricular septal defect was diagnosed. In 6 pts, a Doppler signal was only obtained with the use of contrast.

In 15 pts, a RV/RAg superior to 40 mmHg was only obtained with the use of contrast. Of these, 9 have already been submitted to right heart cathetherism, that confirmed the diagnosis of pulmonary hypertension in 5 of them (56%).RV/RAg (P) was 44+/-11 mmHg and RV/RAg (PC) was 54+/-11 mmHg, p<0,001.

Conclusions: 1. The method is applicable in a large number of patients.

2. RV/RA gradients obtained at peak exercise are higher with the use of contrast, and the clinical meaning of this difference should be evaluated in a larger number of pts submitted to right heart cathetherism.

The high number of false positives should lead to a higher diagnostic threshold. 3.

This method seems to have relevant clinical value in the diagnosis of pulmonary arterial hypertension.

 AuntMinnie.com Oct 13, 2008 Acusphere's Imagify to get FDA review 
Ultrasound contrast developer Acusphere said that its Imagify contrast agent will be reviewed during a planned public meeting of the U.S. Food and Drug Administration (FDA)'s Cardiovascular and Renal Drugs Advisory Committee on December 10. 
(Full article available by subscription)

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