Mapping Improvements in Molecular Imaging

Software advances enable fusion of separate PET and diagnostic CT to enhance clinical decisions. This image was generated with MIMfusion software by MIMvista.

“Here’s an analogy,” says Karthik Kuppusamy, general manager of molecular imaging for GE Healthcare (Waukesha, Wis). Drawing on the typical weather report, he likens hybrid imaging to the combination of a geographic map and Doppler radar. “Lots of color over Milwaukee indicates that the weather is active there,” he says. Fusing PET or SPECT with CT, medical imagers can do the same thing in the human body, pinpointing disease before it has made an anatomic impact. New technological advances can even tell healthcare providers how the “cloud” is moving.

“Molecular imaging plays a fundamental role in the prediction, early diagnosis, and provision of a variety of treatment options for physicians so that patients can benefit right away,” Kuppusamy says.

Nuclear medicine has evolved into molecular imaging by nature and by force. Because it can detect metabolism and image disease, molecular imaging is enabling physicians to approach illness differently. “People are living longer, not just because of earlier diagnosis, but also because of intervention,” says Martin Sandler, MD, president-elect of the Society of Nuclear Medicine (SNM of Reston, Va) and chairman of radiology and radiological sciences at Vanderbilt University Medical Center (Nashville, Tenn).

Nuclear medicine has moved to areas where other modalities cannot. “Molecular applications have moved away from traditional anatomy. Roughly 50 percent of nuclear medicine has been cardiac?looking for abnormalities in the walls of the heart. But some of these more traditional applications are being taken over by other modalities, such as MR and CT. As they’ve gotten better, they’ve forced nuclear medicine more into molecular imaging, where nuclear medicine excels,” says Samir Chowdhury, PhD, VP of clinical imaging for Gamma Medica-Ideas Inc (Northridge, Calif, and Oslo, Norway).

As for the future, it’s clear skies ahead. In fact, according to Chowdhury, the industry is moving to better image the exact processes or disease states that are present. “We want to be much more specific in imaging diseases instead of just the structure,” he says.

Members of the industry are achieving this goal in a few ways. One is to advance the technology of nuclear medicine to acquire images more quickly and without compromising image quality. Another is to combine this technology with other modalities, creating hybrids that produce clearer, more accurate pictures. A third method is to develop application-specific systems, both advanced and/or hybrid, that provide specialists with greater economic and clinical value.

Software Improvements with Resolution Recovery

“Usually in nuclear medicine, there are trade-offs between image quality and time,” says Shuli C. Shwartz, PhD, MBA, co-founder and CEO of UltraSPECT Inc (Brookfield, Wis). “If you want better quality, the patient needs to lie still longer?15 to 40 minutes where the patient cannot move. On the other side, if you use a shorter scan time, you are likely to compromise image quality.”

New processing technologies, primarily variants of resolution recovery, are emerging that will enable users to obtain better image quality in shorter scan times. “Resolution recovery will be the dominant technology in the market pretty soon,” Shwartz exhorts?although, she admits, UltraSPECT’s patented wide-beam reconstruction (WBR) will be just one among others.

The underlying idea of WBR is to model the emission-detection process more accurately. “Current technology makes some assumptions and doesn’t take into account certain factors in the process of emission and detection. For example, gamma cameras have collimators, which limit the resolution because of the way they are structured. If you consider the geometry of the collimators, you can improve the image resolution but might enhance noise in the image,” Shwartz says. Simultaneous accounting for the collimator geometry and noise enhancement are key to WBR technology.

Used with existing SPECT systems, WBR can reduce by half the scan time for cardiac SPECT perfusion scans, as well as SPECT and planar bone scans. Stepping up the nuclear-medicine portion of a hybrid exam is key to hastening the entire process. Currently, it is the PET or SPECT scan that takes longest; with higher-slice CT models, acquisition of anatomical data is quick. WBR is an algorithm available as a software product that can be used to speed both stand-alone and hybrid systems.

Hardware Headway

Hardware solutions exist as well. Both Chowdhury and Sandler cite different products that combine similar advances in hardware along with new algorithms to produce quality images in less time and within less space.

GE Healthcare has introduced a number of products that incorporate the new nuclear-medicine technology, including the Ventri, a nuclear imaging system; the Discovery VCT, which fuses PET with 64-slice CT; and the Infinia Hawkeye 4, a gamma camera and 4-slice CT hybrid that received FDA clearance in late 2005.

“We’ve moved to the next-generation technology of fully solid-state detectors, which use cadmium zinc telluride, or CZT. Gamma photons are converted into electrical energy with no light in between. These detectors are very stable and pixilated to a resolution of 1.6 millimeters,” says Gamma Medica’s Chowdhury, who notes that the contrast resolution also is improved due to the detector’s 4.5% energy resolution. Better spatial and contrast resolution produce a better image.

Above left is a cardiac perfusion scan acquired in 10 minutes using filtered backprojection reconstruction (FBR) technology; above right, another scan of the same patient acquired in 5 minutes using UltraSPECT’s WBR technology.

Spectrum Dynamics Ltd (Tirat Hacarmel, Israel) uses a different technology, according to Sandler, who sits on the company’s advisory board. A bank of 10 columns of solid-state CZT detectors participates in the data collection, permitting the acquisition of a cardiac scan in 2 minutes with 10 times the sensitivity and about twice the resolution of conventional scintillation camera technology, Sandler explains.

“The advance opens opportunities. One is that the rapid acquisition now matches that of CT, so we can do a two-minute cardiac perfusion scan, look at it, and decide whether the patient should have an additional scan while on the table,” Sandler says. The benefit of these sequential scans is that the patient remains in one position, as opposed to scanning later and trying to match the images. The result is a clearer picture that contributes a more accurate diagnosis.

Another opportunity is the potential to measure blood flow. “Being able to capture images in such a short time frame allows you to potentially look at blood-flow measurements, which opens up the next paradigm of imaging?to be able to quantitate blood flow,” Sandler says. “It changes the whole environment of imaging.”

Radiopharmaceuticals Renovation

Developers of the acquisition and processing systems are not the only ones who are making advances; perhaps they are not even the most eagerly anticipated. Radiopharmaceuticals also have been in development, and new biomarkers finally are poised to enter the marketplace.

“There are not new radiopharmaceuticals coming out all the time. We haven’t had new PET markers in quite a long time,” says Kevin Berger, MD, director of PET/CT at Michigan State University (East Lansing). He notes that the markers many currently use in practice are actually in developmental research, and he believes that growth in these products is necessary to move the field forward.

Berger is not alone. “I think the advantages of molecular imaging are not limited by instrumentation but by radiopharmaceuticals. As new development in radiotracers occur, whole new areas of diagnosis and investigation will open up,” predicts Dennis Nelson, president of MIMvista Corp (Cleveland). Nelson notes that because radiopharmaceuticals can have specific affinities for tumors and metabolic processes, they expand the capabilities of nuclear medicine?unlike modalities like CT and MR, which are constrained by the physical equipment.

Michael Reitermann, president of the molecular imaging division at Siemens Medical Solutions (Malvern, Pa), anticipates a lot of excitement in new radiopharmaceuticals. “As we understand much better how disease develops in the body?which proteins are expressed in which disease at which stage?we can identify a compound that is attracted to that protein when injected in the body and will accumulate,” Reitermann says. “That allows us to capture what we can identify as indicators of disease.”

PET As Umbrella

The capability that Reitermann describes applies throughout the body, with applications in neurology, cardiology, and oncology. SPECT use worldwide is fairly even among oncology, cardiology, and general imaging, with a small portion applied in neurology. However, PET is used primarily in oncology. (See “SPECT and PET Distribution” )

Siemens Medical, according to Reitermann, views the continuum of care, beginning with prevention and moving through early detection, diagnosis, care, therapy, and follow-up. Nuclear medicine begins to have an impact at the early-detection stage.

MIMneuro provides quantitative analysis for detection of Alzheimer’s disease and other dementias.

“We can detect changes on a molecular level much earlier-before you see anatomical change. This allows you to intervene much earlier,” Reitermann says, offering cancer as an example of how this can benefit patients.

Cancer detected before it has metastasized has a much greater chance of being treated successfully than after it has spread. Molecular imaging, which can help diagnose oncological conditions at this stage, can increase the chances of saving a patient and, therefore, can have a huge impact on care?and not just in oncology, but also for a variety of diseases, including cardiac conditions.

Heart-Stopping Improvements

Nuclear medicine can assess blood flow in the heart muscle, allowing very early detection and understanding of what happens in the heart, according to GE Healthcare’s Kuppusamy.

Molecular imaging will not necessarily prevent cardiac disease, Sandler adds. “There are many dynamics to preventive care, beginning with upbringing, exercise, food, and not smoking,” he says. By helping with early detection, nuclear medicine can improve outcomes through early screening. “We want to pick up patients before they occlude their vessels to prevent the potential risk to life of an acute ischemic episode?we want to find patients at risk of these syndromes before they have them,” Sandler says.

Worldwide, 35% of roughly 40 million SPECT procedures are applied within cardiology; that figure jumps to 55% when the approximately 20 million SPECT procedures in the United States are analyzed. (See “SPECT and PET Distribution“.) Only 4% of PET procedures, both worldwide and nationally, have occurred within cardiology, but PET is poised to increase with new products, such as the Discovery VCT and Ventri systems from GE Healthcare.

Adds MSU’s Berger, “There has been significant growth in cardiac PET?specifically a renewed interest in cardiac perfusion imaging with rubidium and N-13 ammonia.” He credits new software programs with permitting providers to see perfusion deficits in the heart and angiographic correlates noninvasively. “Improved accuracy of PET can reduce the negative diagnostic catheterization rate?25 percent or even more of cardiac catheterizations are negative, meaning the patient didn’t need it,” Berger says. “With improved accuracy, PET can better stratify patients and allow us to intervene only in those who really need it.”

Memory Preservation

PET also can stratify patients with early-onset Alzheimer’s disease even earlier than before. One of the biggest areas poised for growth is this indication. According to MIMvista’s Nelson, several studies have been published by institutions, such as the University of California, Los Angeles (UCLA) and the University of Michigan, that analyzed past brain studies and found that previously “normal” scans actually contained metabolic clues to early onset of Alzheimer’s.

“There may be potential to identify the onset of Alzheimer’s ten years prior to any clinical symptoms,” he says. Because the disease develops so slowly, early interventions that slow its progress even further will have greater success in preserving patients’ mental capabilities.

The ability to better image Alzheimer’s will be aided by new radiopharmaceuticals. “There’s lots of excitement with amyloid imaging. Both carbon and fluorinated PET radiopharmaceuticals that look at amyloid deposition are under investigation. Several groups are at work on markers for beta amyloid. By imaging the regional deposition of beta-amyloid, we might be better able to diagnose and treat Alzheimer’s disease,” Berger says.

Currently, the effect is measured indirectly, through imaging of F-18 fluorodeoxyglucose (FDG) metabolism. “This use is focused and limited?differentiating Alzheimer’s from fronto-temporal dementia,” Berger explains. This use, at least, is covered by the Centers for Medicare and Medicaid Services (CMS of Baltimore). More research and clinical value will be needed before diagnosis of early-onset Alzheimer’s is approved.

Cancer Control

Screening is where nuclear medicine can prove extremely valuable, especially in oncology, where high-risk patients are screened for such conditions as colorectal, breast, and prostate cancers. Mammography is the gold standard for breast-cancer screening and performs very well for most women. However, due to its structural nature, mammography’s effectiveness decreases in women who have dense breasts or scarred tissue (from previous surgeries or breast implants). According to Gamma Medica’s Chowdhury, this population subset represents 25% to 30% of women.

The functional imaging capability of molecular imaging allows it to see through structure and visualize malignant cancer. For high-risk patients (those with a previous incidence or family history of breast cancer) who also have highly structured breast tissue, molecular breast imaging can provide valuable information to supplement the information gained from mammography. In addition, new advances in camera technology have led to high-resolution, high image quality systems that are able to detect smaller lesions. “One third of women have dense breasts,” Chowdhury says. “That’s a significant number of women who can benefit from these high-performance molecular imaging systems.”

Similar improvements can be seen in cancers not traditionally screened, such as bone. UltraSPECT introduced software (Xact.bone) to improve bone scans. “The scan time remains the same, but the resolution is improved. Images are sharper and more focused without enhancing noise,” says the company’s Shwartz. “It enables the physician to better localize lesions, which are sometimes fuzzy.”

SPECT AND PET DISTRIBUTION

Source: IMV SPECT Census Report 2003; IMV PET Census Report 2003; PET and Molecular Imaging Report Europe 2004; SMI CRM Understand and Strategic Planning

Performing With PET

Combining the information with anatomical data derived from a modality, such as CT, can help to guide treatment once the cancer has been localized. Nelson predicts that image-guided intervention will increase “quite a bit. We have all of these techniques for intervening?whether brachytherapy, RFA, cryoblation, or biopsy?and all of them need to identify the tumor well. Molecular imaging, and particularly PET, does a good job,” Nelson says.

Adds Siemens’ Reitermann, “With CT, we can obtain a very detailed picture, down to submillimeter resolution. We can identify the size of the tumor, and, with the capabilities of SPECT and PET, we also can detect the activity level of the tumor.”

If a tumor has been found, Chowdhury notes, nuclear medicine can show whether it has all been removed during surgery. It also can identify if the disease has spread, for example to a nearby lymph node, during surgery for immediate treatment, eliminating the need for additional surgeries. More diagnostic information means that better therapeutic decisions can be made, and patients can experience improved care.

The Forecast

“As we continue to develop quantitative methods for evaluating tumor size, avidity, and metabolism, we’ll see nuclear medicine used more and more as a tool to direct patient management, particularly for cancer. It will have as big an impact on patient care as it has had on diagnosis,” Nelson predicts.

Molecular imaging’s expansion throughout the patient-care continuum is what many forecast as its future. Of course, it won’t get there alone; its greater clinical value will come from fusion with other modalities, such as CT and MRI. (See “MRI Hybrids March On” below for more information about fusion imaging). However, its effect will be revolutionary all the same.

“The technological advancements will have an enormous impact on the next era of molecular medicine. In 20 to 30 years, those able will look back and see that medicine completely changed, both the delivery of healthcare and the management of patients,” Sandler prophesizes.

The industry is ready. Shwartz notes that scan time was shortened about 12 to 14 years ago when the industry moved from the single-detector gamma camera to dual-detector systems. “Since then, there have been no new methodologies, algorithms, or hardware for substantially reducing the scan time,” she says. But that is about to change. And with the new batch of methodologies, algorithms, hardware, and radiopharmaceuticals, nuclear imaging will find itself on the map.

Wren Davis is a contributing writer for Medical Imaging.