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The latest developments in multimodality imaging

The technologies in multimodality imaging are improving at such a rapid speed that the question is whether we are able to keep up

Alberto Cuocolo MD, Department of Biomorphological
and Functional Sciences, University Federico II, Naples,

New multimodality imaging systems such as positron emission tomography (PET)–computed tomography (CT), single-photon emission computed tomography (SPECT)–CT and PET–magnetic resonance (MR) bring together anatomical and molecular information and carry enormous potential for rapid and efficient diagnosis, but also challenge established patterns of professional practice and patient care. Radiological imaging with multislice CT provides excellent and detailed anatomical information in a short time. However, structural changes are the result of disease processes and became evident only when the disease has progressed significantly.

However, nuclear medicine imaging techniques provide functional and physiological information and may detect pathophysiological changes occurring before structural changes are evident. However, it should be considered that one of the major limitations of nuclear medicine is that this targeted approach sacrifices anatomical details that are needed for accurate interpretation of the information.

Over the last few years, SPECT and PET have become accessible to a large number of clinical centres for diagnostic purposes. SPECT and PET use a variety of radiopharmaceuticals to obtain in-vivo images of the biochemistry of disease. PET and SPECT scanners have now been linked to CT scanners, which are digital radiological
systems that acquire data in the axial plane, producing
images of internal organs of high spatial and contrast resolution.

The combination of PET or SPECT and CT as a single unit provides spatial and pathological correlation of the abnormal functional and/or metabolic activity, allowing images from both systems to be obtained by a single instrument in one examination procedure with optimal co-registration of images. The resulting fusion images facilitate the most accurate interpretation of both PET or SPECT and CT studies. CT attenuation maps from these integrated systems are used for rapid and optimal attenuation correction of the PET or SPECT images. In addition, PET-CT and SPECT-CT images are used to improve radiotherapy planning and to guide intervention. This
process of integration of imaging systems has progressed to MR.

Optimal CT protocols for use in combination with PET and SPECT are being developed. These include the administration of appropriate contrast agents to avoid attenuation artifacts and optimal procedures to minimise potential mismatches due to respiration and patient positioning between PET and SPECT and CT examinations. Respiratory and cardiac gating devices are under development.

The CT component of PET-CT has now evolved to a fully diagnostic, contrast-enhanced CT examination.

Research in the field of imaging has become a multidisciplinary process, with radiologists and nuclear medicine specialists working not only with clinicians from other disciplines but also with physicists, biochemists, physiologists, computer experts and bioengineers.

SPECT-CT systems
Functional imaging with SPECT has the limitations of poor anatomical resolution as well as nonspecificity. Various methods of co-registration have been developed to improve anatomical localisation. Initial attempts resulted in the development of dedicated software to co-register results of studies performed separately by different modalities such as SPECT and CT.

However, to reproduce the exact positioning between different modalities is very difficult. This led to the development of dedicated single-gantry emission–transmission imaging systems using an array of high-purity germanium detectors as well as SPECT-CT scanners.

As the study is performed on the same equipment in registered format without changes in patient position, it allows superimposition of the SPECT images with CT images without the challenge of co-registration of results from different patient positioning. The transmission data obtained with the CT component are also used for attenuation correction of images acquired by SPECT.

New generations of hybrid SPECT-CT systems utilise multidetector spiral CT allowing for better anatomical resolution, greater contrast and quicker scan times.

PET-CT systems
Today, the very large majority of the new PET scanners installed are combined with multidetector CT scanners capable of acquiring up to 64 slices in one rotation. Excellent anatomical details acquired by these scanners, such as those obtained from CT coronary angiography, can now be combined with functional/physiological imaging, such as myocardial perfusion study, allowing for better diagnostic accuracy.

In order to generate an accurate, concise report for images acquired from these newer generations of hybrid systems, the nuclear medicine physician needs to be comfortable interpreting the diagnostic component of CT obtained with
oncological PET as well as CT coronary angiography obtained with the myocardial perfusion study.

At present, 18F-fluorodeoxyglucose is the only PET radiopharmaceutical that is widely available for human use. 11C-labelled compounds are confined to research centres with cyclotron capabilities, while active investigations have
been conducted to develop other 18F- and 68Galabelled
radiopharmaceuticals that are now entering clinical studies.

PET is currently the most powerful molecular imaging techniques used in clinical diagnosis, although developments in MR are progressing rapidly. However, unlike MR, PET images often lack anatomical landmarks and are interpreted in correlation with images obtained by anatomical imaging modalities in order to locate more precisely the regions of abnormal metabolic signal or enhanced/reduced tracer uptake.

PET-MR systems
SPECT-CT and PET-CT systems have some limitations, including the inability to perform simultaneous data acquisition and the significant radiation dose to the patient contributed by CT. MR imaging offers, as compared with CT, better contrast among soft tissues and higher functional-imaging capabilities. Therefore, the combination of PET with MR provides many advantages that exceed the combination of functional PET information with anatomical MR data. However, many technical challenges, including possible interference between the two modalities, have to be solved when combining PET and MR, and various approaches have been proposed to overcome these limitations.

The initial results achieved with animal PETMR systems and the first clinical PET-MR brain imaging system demonstrate the feasibility of simultaneous data acquisition with insignificant interference between the two systems.

Another potential capability of integrated PET-MR is represented by the possible temporal and spatial correlation of functional data derived by MR spectroscopy and functional imaging by PET. Thus, the combination of PET and MR is a promising tool in preclinical research and will progress to clinical application in the near future.

Indications for multimodality imaging Oncological diseases
Diagnostic PET-CT, SPECT-CT and ultimately PET/SPECT-MRI are integrated diagnostic procedures with very powerful capacities to determine tumour spread when used by physicians who understand and are trained in imaging methodologies, tumour biology, treatment options and
the functional changes induced by the various therapeutic procedures. In addition, response evaluation appears to be a major indication for multimodality imaging. For the moment it is mainly used to assess prognosis, but in the future it might be broadly used to guide patient management based on the individual response pattern.

Finally, improved preoperative localisation of tumour spread will greatly assist the interventional radiologist and surgeon, who may be further helped by intraoperative probe detection of tumour deposits. Biopsies might also be guided by these combined imaging modalities, which can indicate and localise the part of the tumour with the highest density of proliferating cells. These methods improve radiation oncology by determining the biological target volume.

Neurological diseases
With new treatments for dementia being developed, it is extremely important to identify objective reproducible parameters of response. Hybrid brain imaging has the potential to play an important role in the diagnosis and follow-up of dementia. Furthermore, studies of neuronal transporters and receptor mechanisms by hybrid brain imaging allow confirmation of the diagnosis, disease staging and assessment of the effect of treatment in Parkinson’s disease and other neurodegenerative disorders.

Cardiovascular diseases
The major advantage of the integrated approach to the diagnosis of coronary artery disease is the added sensitivity of PET or SPECT and CT angiography. As not all coronary artery stenoses are flow-limiting, PET or SPECT stress perfusion imaging complements the anatomical CT data by providing functional information on the haemodynamic significance of such stenoses, thus allowing more appropriate selection of patients who may benefit from revascularisation procedures.

While the principle may be the same, each modality has its specific benefits. Earlier studies conducted with three-dimensional image fusion of CT and SPECT showed promising results.

One of the major uses of SPECT-CT is the production of better attenuation correction. Apparent perfusion defects occur most often in the anterior wall in women and in the inferior wall in men, and soft-tissue attenuation can also shift between resting and stress images. Interpreting these examinations requires clinicians to recognise any attenuation artifacts and allow for them in evaluating the underlying perfusion pattern.

In addition to being intuitively convincing, these images provide a panoramic view of the myocardium, regional myocardial perfusion and the coronary artery tree, thus eliminating uncertainties in the relationship of perfusion
defects and stenotic coronary arteries in watershed
regions. This may be particularly helpful in patients with multiple perfusion abnormalities and complex coronary artery disease.

Similarly, the integration of PET and CT scanners enables detection and quantification of the burden of calcified and noncalcified plaques, quantification of vascular reactivity and endothelial health, and identification of flow-limiting
coronary stenosis.

Integrated PET-CT also offers an opportunity to assess the presence and magnitude of subclinical atherosclerotic disease burden and to measure myocardial blood flow as a marker of endothelial health and atherosclerotic disease activity. Because not all coronary stenoses detected by CT are flow-limiting, the stress myocardial perfusion PET data complement the CT anatomical information by providing instant readings about the clinical significance of such stenosis.

Other diseases
Multimodality imaging has also been shown to be of value in the diagnosis of other conditions, such as infection and inflammation. However, further studies are needed to refine these technologies, address the issue of cost-effectiveness and validate a range of clinical applications in large-scale clinical trials.

Finally, it should be stressed that, although these new multimodality imaging systems carry enormous potential for rapid and efficient diagnosis, they also challenge established patterns of professional practice and patient care.

These new developments will demand a high level of training in both nuclear medicine and radiology for high quality of interpretation of the images generated by these hybrid systems. Therefore, steps to accommodate the special needs required to interpret the images generated by these hybrid systems must be taken. As nuclear medicine and radiology have now entered the era of molecular imaging, physicians will need to be trained in looking at both the anatomical component and the molecular/physiological component and provide an accurate concise diagnostic report generated by these hybrid systems.