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However, multimodality systems typically come with trade-offs that have to be balanced against the perceived added value. Possible negatives and other considerations include: i any reduction in imaging performance compared with stand-alone system, ii system cost if greater than the individual components, iii space requirements, iv additional operational complexity increased downtime? Yet the history of this example also serves to illustrate that it is not easy to predict the impact of a hybrid system until it has been developed sufficiently to be applied to biomedical or clinical problems.
Therefore, it is important that research into the development and optimization of new hybrid imaging systems continue to be supported, as it offers one of the best opportunities for major technical innovation and impact in contemporary medical imaging science.
Molecular Anatomic Imaging: PET-CT and SPECT-CT Integrated Modality Imaging - Google книги
In part, this was due to the substantial difficulties posed by operating these systems in close proximity, and in part due to initial lack of industry interest and concerns over the cost of such a combined device. This opens up a wealth of interesting research opportunities, and with these advanced MR techniques finding increased clinical utility, there likely will be range of clinical applications that combine anatomic MR, some form of functional MR measurement and molecular imaging with PET or SPECT.
This is of particular importance for studies that are monitoring disease progression and response to therapy with multiple scans. While these are all good reasons for developing hybrid systems with MR rather than CT, there is one significant drawback of MR that must be acknowledged.
MR does not directly provide the information required for attenuation correction of the nuclear medicine study. In particular, it is challenging to separate air and bone, and to measure the density variations in the lung with MRI. This is a radical departure from the approach used for fusion with CT, where the scanners were arranged in a tandem rather than concentric configuration, and where scans were acquired sequentially.
The PET or SPECT system must operate in a high magnetic field environment, which suggests the use of scintillators coupled to magnetic field insensitive solid state light detectors such as avalanche photodiodes [ 29 , 30 ] or silicon photomultipliers [ 31 ]. Alternatively, if traditional photomultiplier tubes are to be used, they need to be placed outside of the magnet in an area where the fringe field is low enough that they can be effectively shielded against the field [ 20 , 32 , 33 ].
The MRI system requires very good uniformity of its magnetic field typically 1 part in 10 6 or better and foreign objects placed in or around the magnet have the potential to perturb that field. The third and generally most challenging issue relates to electromagnetic interference between the two systems.
An MRI system generates high power radiofrequency pulses, as well as rapidly switching gradient magnetic fields. It is very easy for these signals to be picked up by the PET or SPECT system, swamping the low amplitude signals produced by the scintillation detectors. It also is very possible that components of the PET and SPECT electronics such as the power supplies or preamplifier electronics radiate electromagnetic waves that can interfere with the MR signals.
Firstly, any moving parts are very likely to create artifacts in the MR images, and therefore traditional rotating gamma camera systems are problematic. Despite these not inconsiderable difficulties, the field has advanced quite impressively in the last 2—3 years. Two MR-compatible PET scanners based on avalanche photodiode detector technology have been developed for small animal imaging and have been successfully applied for a range of in vivo applications [ 22 , 23 ].
A variety of other designs also are at various stages of development [ 32 , 34 , 35 ] including some approaches that involve modifications to the MR system such as split magnet designs [ 36 ] and field-cycled systems [ 37 ]. The first successful systems have been built, but there is much debate and little consensus what the ultimate role for this powerful hybrid imaging technology will be [ 38 — 40 ].
Time will tell. Given the tremendous opportunities presented by integrating in vivo imaging modalities with different strengths, it is not surprising that several other hybrid combinations are being explored. Some of these are primarily directed at small animal research for example many of those involving optical imaging techniques , but may nonetheless ultimately find some application in the clinic.
Here we briefly summarize a small selection of other hybrid imaging systems under development, focusing on the motivation for their development and possible applications. This merger of two molecular imaging technologies is motivated by the desire to measure multiple molecular targets simultaneously, and by the need for imaging technologies that can serve as a translational platform between the very widely used optical techniques that employ bioluminescent or fluorescent reporter genes, or injected fluorescent probes, in small animal models [ 41 ], and nuclear medicine radiotracer assays that can be moved from mouse to human [ 42 ].
There also is interest in merging two structural imaging techniques for interventional applications. X-ray fluoroscopy has very high spatial and temporal resolution, but provides only two-dimensional images, whereas MRI, although slower, provides 3-D images that can significantly aid in accurate localization.
A prototype x-ray fluoroscopy system has been constructed in the bore of a vertical gap interventional MR scanner and successfully deployed for patient studies, with applications including placement of vascular shunts in the liver, arthrograms, prostate seed implantation, arteriovenous malformations and cystography [ 47 ]. A system integrated with a short closed-bore system is being developed consistent with the trend towards the use of these higher field MR systems for interventional applications [ 47 ].
Uniquely, this hybrid technology relies on the interaction of two imaging modalities, optical imaging and ultrasonic imaging, to take advantage of the high spatial localization capabilities of ultrasound at depth in tissues, and the high sensitivity provided by optical contrast [ 48 , 49 ].
Tissue is excited with a short-pulsed laser beam and absorbed locally by endogenous chromophores such as hemoglobin, or by administered optical contrast agents. Absorption of the light by the chromophore results in small amount of local heating, which is converted to a rise in pressure due to thermoelastic expansion of the tissue. This pressure rise propagates as an ultrasonic wave through tissue and can be detected by an ultrasound transducer. In animal models, this technique allows very high spatial resolution functional and molecular imaging to be obtained at depths of several mm beneath the surface [ 50 ].
This technique can provide images of the vasculature, hemoglobin concentration, hemoglobin oxygen saturation, metabolic rate of oxygen and melanin concentration by measuring the absorption of light by native chromophores. Using optically-absorbing targeted contrast agents, it may also be possible to image the distribution of molecular targets and gene expression. Photoacoustic tomography is being explored for a range of clinical applications, including breast imaging, melanoma detection, sentinel lymph node analysis, endoscopic applications, and even brain imaging [ 48 — 50 ].
In vivo optical imaging at any significant depth in tissue typically carries little in the way of structural information and thus, similar to the rationale behind integrating PET or SPECT with CT or MRI, there are good reasons to develop optical imaging in conjunction with high resolution 3-D structural imaging. Applications range from small animal imaging to human breast and brain imaging.
Given the ill-posed nature of the data available to reconstruct 3-D diffuse optical tomography or fluorescence tomography images, the spatially registered MR images can be employed to delineate the boundaries of tissues with different optical properties, and thus potentially improve the accuracy of the 3-D optical reconstructions. A number of large biomolecules e. One motivation for developing these hybrid agents is that they enable one to study the same target, with the same imaging agent, on different imaging platforms and at different scales.
For example one could take a multimodality agent and do fluorescence imaging in cell culture and small animal models, and then using the same agent perform MRI, PET or SPECT in larger animals or patients. A second possibility is that these agents could be used with multimodality instrumentation.
Examples include fluorescent quantum dots with a paramagnetic coating [ 52 ], quantum dots with high native relaxivity [ 53 ], lipoproteins incorporating iron oxide nanoparticles and quantum dots [ 54 ], liposomes containing Gd and fluorescent agents [ 55 ] and antibodies conjugated with both nanoparticles and fluorescent agents [ 56 ].
In some cases, these particles and proteins are additionally being designed to incorporate radionuclide tags for PET or SPECT imaging [ 25 , 42 , 57 , 58 ]. Ultrasound contrast agents also are being used as a basis for multimodality agents. Microbubbles provide high contrast for ultrasound imaging, and their lipid shells can be labeled with radionuclides or fluorescent agents for multimodality ultrasound-optical-PET detection [ 59 ].
Clearly, multimodality imaging is thriving and still evolving rapidly. Multimodality imaging agents offer a powerful way to interrogate biological targets in vivo using a range of imaging modalities and are highly complementary to the hybrid imaging systems that are being developed. Finally, another important area of integration, not discussed here, is the interface between imaging and disease treatment. There has been huge progress in instrumentation designed for imaging concurrently with radiation therapy and interventional procedures, and in new imaging agents designed to help monitor chemical, biologic and genetic therapies.
The integration of structural, functional and molecular imaging with therapeutic intervention represents the ultimate multimodality platform for biomedical research and eventual clinical application. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
PET generally has excellent sensitivity, while CT detects small lung nodules more accurately. FDG uptake has the ability to distinguish residual tumour activity from scar tissue in residual masses after chemotherapy. An integrated approach is essential in the assessment of neuro-endocrine tumours NETs. The final diagnostic analysis combines functional, morphological and positional information.
Molecular anatomic imaging 3rd
A detailed radiological work-up is only possible once a functional lesion has been localised. Localisation of well-differentiated NETs is performed by using labelled analogues of somatostatin, or molecules concentrated by NETs. Bone scintigraphy is a first-line technique for surveying the entire skeleton for metastases in patients with cancer of the breast and prostate, as well as small-cell lung carcinoma.
While highly sensitive, the specificity is reduced by numerous benign processes e. Here, radiology has a long-established complementary role, as local radiographs of these sites identify most benign causes of increased activity, whereas normal radiographs are suggestive of metastatic disease. T1 changes appear up to three months before other modalities are positive; 4 however, MRI studies are limited by cost and a small field of view, disqualifying it as a viable screening alternative to bone scintigraphy. T1-weighted MRI sequences should be reserved for specific clinical problems, e.
Diffusion-weighted whole-body MRI is an exciting new development with promising results for cancer detection, widely reported in the recent literature. Bone scintigraphy plays a complementary role in benign bone disease, adding sensitivity and enabling an entire skeletal survey. Most fractures are diagnosed using conventional radiographs, but bone scanning is a cost-effective and sensitive means of detecting fractures, which have a normal appearance on plain films e.
Scintigraphy also allows localisation of sites causing back, ankle or foot pain. When there are subtle or multiple anatomical abnormalities, active osteoblastic activity can direct therapeutic interventions to sites requiring relief of pain Fig. Acute osteitis in children can present challenging diagnostic dilemmas.
These children often present as emergency cases, acutely ill and with raised inflammatory markers. The presenting complaint may, however, be limited to diffuse bone pain with normal erythrocyte sedimentation rate ESR and white blood cell WBC counts. Plain film examination of the affected limb should precede special investigations. Ultrasound is an excellent first-line investigation and is often diagnostic Fig. CT is an acceptable alternative, but an MRI study, when available, is definitive, showing the extent of trabecular oedema and soft-tissue involvement.
Skeletal scintigraphy remains particularly valuable when MRI availability is limited, symptoms are poorly localised, or multifocal disease is suspected. Ultrasound is normally the first line of investigation, but MRI, with its superior soft-tissue discrimination, is the investigation of choice.
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Inflammatory processes are identified by a hyperintense signal on T2 STIR or post-contrast T1 fat saturation sequences. However, an altered anatomy because of previous trauma or surgery may render findings equivocal. These tracers are specific and sensitive, demonstrating inflammatory processes before anatomical changes occur. The choice of technique depends on the suspected site and chronicity of the infection.
CTPA is based on the direct detection of emboli presenting as filling defects in affected vessels, while VQS images the functional consequences of the emboli, i. VQS, using new interpretation criteria, achieves excellent sensitivity and specificity with few equivocal studies, and today should be utilised by all nuclear medicine units. Specific considerations such as compromised cardiorespiratory function or structural lung disease favour the use of CTPA when both modalities are available.