System and Apparatus for Multimodality-compatible High-quality Intravital Radionuclide Imaging

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ABSTRACT:The present invention discloses an imaging system and apparatus to obtain high-resolution low-noise intravital radionuclide imaging based on transparent window chamber. This imaging system is dedicated to preclinical research. It comprises a transparent window chamber, in particular a dorsal skin window chamber or a cranial chamber or an ear chamber or a spine cord chamber on a living animal, and a high-quality radionuclide imaging camera for the imaging of positron or electron. The apparatus is compatible with multimodality imaging, in particular magnetic resonance imaging (MRI), microscopy imaging including fluorescence microscopy, phosphorescence microscopy and two-photon microscopy.

DESCRIPTION:The present invention discloses an imaging system and apparatus to obtain high-resolution low-noise intravital radionuclide imaging based on transparent window chamber. This imaging system is dedicated to preclinical research. It comprises a transparent window chamber, in particular a dorsal skin window chamber; cranial chamber, ear chamber or spine cord chamber on a living animal and a high-quality radionuclide imaging camera for the imaging of positron or electron. The apparatus is compatible with multimodality imaging, in particular magnetic resonance imaging (MRI), microscopy imaging including fluorescence microscopy, phosphorescence microscopy and two-photon microscopy.

The system of the present invention enables a reliable link between macroscopic imaging and microscopic physiological measurements. It allows high quality radionuclide imaging, high compatibility with multiple imaging modalities, precise co-registration of images obtained from different sources at different times and intact longitudinal multimodal observation. Thus the present invention can assist the validation and development of pharmaceutical, imaging, diagnostic and therapeutic techniques and strategies.

In contrast to conventional anatomical imaging such as CT or MRI, molecular imaging extends the clinical frontline to fundamental molecular pathways in organisms noninvasively, which supports the individualization of healthcare. Among all the molecular imaging modalities, radionuclide imaging such as positron emission tomography (PET) or single photon emission computed tomography (SPECT) are most widely used in clinical practice due to their high sensitivity of physiological differences and have shown enormous clinical value for example in early detection of cancer, staging, localization and therapy prognosis.

Radionuclide imaging is achieved through injection of radiolabeled molecular biomarkers, which generate contrast between normal and abnormal tissues according to their different metabolic properties of the injected biomarker. Various biomarkers have been developed for the detection of different physiological functions such as glycolysis (e.g. [18F]FDG, 99mTc-HMPAO), perfusion (e.g. [13N]Ammonia, 99mTc-tetrofosmin), hypoxia (e.g. [18F]Fmiso), proliferation (e.g. [18F]FLT) and so on.

The radioactive signals emitted from the radiolabeled biomarkers can be detected by radiation cameras (Scintigraphy), SPECT for single photon emitters or coincidence detectors (PET) for positron emitters.

After injection into the body, molecular biomarkers are delivered through macro- and microcirculatory system into tissues and then get either metabolized in the target area or cleared out. This complex procedure causes the acquired image to be influenced by many confounding factors, such as vascular delivery, interstitial transport and renal clearance. The interpretation of molecular imaging towards characteristics of the tumor microenvironment is therefore not straightforward.

For pharmaceutical development of new imaging biomarker or the application of clinical diagnosis and therapy planning, the assessment and validation of molecular imaging and its evaluation methods is necessary.

The assessment of molecular images requires a reliable link from macroscopic imaging to microscopic measurements. However, such a reliable link is not straightforward.

Conventionally, tumors need to be resected after animal scarification and be cut into sections for the investigation by microscopy. Although these in vitro methods have been widely used in various applications, they are destructive and have limited ability to provide insight into in vivo dynamics. The inconsistency between in vivo and in vitro does not meet the requirements for clinical applications such as biologically guided radiotherapy.

Furthermore, there exists a huge difference between typical preclinical and clinical molecular images (˜mm) and microscopic measurements (˜μm). The current preclinical PET can reach a resolution of approximately 1 mm while the preclinical SPECT can achieve 0.4 mm resolution for small animals. The measured signal in an imaging element is an integration of the signal over a relatively large scale of heterogeneous tumor microenvironment, which makes the validation of molecular imaging even more difficult.

The resolution of current radionuclide imaging devices is relatively low compared to morphological imaging modalities. For preclinical research of radionuclide imaging, high resolution is preferred.