What Student Need to Know about Molecular And Functional Imaging In Radio-Diagnosis.

 What Student Need to Know about Molecular And Functional Imaging In Radio-Diagnosis.

Magnetic resonance imaging (MRI) has been applied to many aspects of functional and molecular imaging. Many of the parameters used to produce image contrast in MRI are influenced by the local chemical environment around the atoms being imaged; these parameters can be exploited to probe the molecular content of tissues and this has been shown to have many applications in radiology. Diffusion-weighted imaging is a well-established method for measuring small changes in the molecular movement of water that occurs following the onset of ischaemia and in the presence of tumours. Exogenous contrast agents containing gadolinium or iron oxide have been used to image tissue vascularity, cell migration, and specific biological processes, such as cell death. MR spectroscopy is a technique for measuring the concentrations of tissue metabolites and this has been used to probe metabolic pathways in cancer, in cardiac tissue, and in the brain. Several groups are developing positron-emission tomography (PET)-MRI systems that combine the spatial resolution of MRI with the metabolic sensitivity of PET. However, the application of MRI to functional and molecular imaging is limited by its intrinsic low sensitivity. A number of techniques have been developed to overcome this which utilize a phenomenon termed hyperpolarization; these have been used to image tissue pH, cellular necrosis, and to image the lungs. Although most of these applications have been developed in animal models, they are increasingly being translated into human imaging and some are used routinely in many radiology departments.

Molecular imaging is a rapidly developed multidiscipline which involves molecular biology, chemistry, computer, engineering, and medicine. It can realize noninvasive and real time visualization, measurement of physiological or pathological process in the living organism at the cellular or molecular level. And it also allows repeated studies in the same animal, thus making it possible to collect longitudinal data and reduce the number of animals and cost. Therefore, molecular imaging plays an important role in earlier detection, accurate diagnosis, and drug development and discovery. Molecular imaging requires high resolution and high sensitive instruments to detect specific imaging agents that link the imaging signal with molecular event.

There are five imaging modalities available for molecular imaging, including X-ray computed tomography imaging (CT), optical imaging (OI), radionuclide imaging (involving PET and SPECT), ultrasound (US) imaging and magnetic resonance imaging (MRI). In the past two decades, imaging instruments have grown exponentially. Improvement in instruments and iterative image reconstruction has resulted in high resolution images that reveal tiny lesion and realize accurate quantification of biological process. A parallel development has been the preparation of imaging agents which can bind their targets with high specificity and affinity. In this review, we will discuss the characteristics of molecular imaging, some novel imaging agents based on nanoparticles including targeted imaging agent and multifunctional imaging agents, and cite some examples of their application in molecular imaging and therapy.

Radionuclide Imaging

Radionuclide molecular imaging including PET and SPECT is the earliest and most mature molecular imaging technique. Due to its advantages of high sensitivity and quantifiability, radionuclide molecular imaging plays an important role in clinical and preclinical researches. Over the past decade, with the progress of molecular biology and radiochemistry, a variety of tracer with high specificity and affinity appeared. A lot of preclinical and clinical studies have confirmed the feasibility of using radionuclide molecular imaging to detect tumor and predict response to therapy.


PET is the molecular imaging modality most extensively used in current clinic routine. It measures the signal originated from the radioactive decay of neutron-deficient radioisotopes (such as 11C, 15O, 18F, and 131I) that are intravenously injected into the body. These isotopes emit positrons which are ejected from the nucleus as a result of springless interactions with electrons in surrounding tissue. The positrons rapidly lose kinetic energy by spreading around the tissue and collide with an electron to form two 511 keV photons which are taking trajectory 180° apart, and this is an event known as annihilation. A PET detector surrounding the subject is designed to detect the signal and convert the resulting electrical signal into sinograms that are finally rebuilt into tomographic images.


Unlike PET, SPECT directly detects gamma-ray photon emitted by the chosen radionuclide during their decay. Compared with PET, SPECT is more affordable and extensively employed in the clinical routine, but it is generally less sensitive since the photons which are not traveling along the axis of the collimator are rejected by the scanner. The spatial resolution (8–10 mm) of SPECT is lower than that of clinical PET (5–7 mm), but the spatial resolution of small animal SPECT (micro-SPECT) is higher than that of PET due to the development of imaging equipment. Thus, micro-SPECT is more available in preclinical investigations including the transformation research and animal studies such as oncology, neurology, cardiovascular disease, and drug development. Additionally, since the radionuclides commonly available for SPECT have longer half-life periods (ranging from a few hours to days), longitudinal studies can be performed. Based on the isotope-specific energies of the emitted photons (e.g., [111In] indium: 171 and 245 keV; [177Lu] lutetium: 202 and 307 keV), SPECT can distinguish different radioisotopes, therefore making it possible to image different targets simultaneously.

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a highly versatile imaging modality. During the past decades, improvement in instrument launched the field of MRI into a new era of molecular imaging. The merits of MRI as an imaging modality for molecular imaging are relatively high temporal and spatial resolution, excellent tissue contrast and tissue penetration, no ionizing radiation, noninvasiveness for serial studies, and simultaneous acquisition of anatomical structure and physiological function. Nevertheless, molecular MRI is limited by its relatively low sensitivity, and this requires the introduction of imaging agent and development of powerful signal amplification strategies. Imaging agent design is hence an important topic in molecular MRI. Currently, the MR imaging agents are mainly divided into two kinds: ferromagnetism contrast agents and paramagnetic contrast agents. The former is considered as negative contrast agents which mainly reduce the signal in T2-weighted images, while the latter is referred to as positive contrast agents that increase the signal in T1-weighted images.

X-Ray Computed Tomography Imaging

CT imaging technologies have undergone a very fast development in the last years. High resolution small animal CT (micro-CT) has transformed CT imaging from organ, tissue to molecular level, which is playing an increasingly important role in preclinical researches. The main advantages of CT are high spatial resolution (micro-CT is 0.020.30 mm; clinical CT is 0.52.0 mm), fast acquisition time, relative simplicity, availability, excellent hard-tissue imaging. Due to limitations like ionizing radiation, limited soft tissue resolution, and poor sensitivity (10−210−3 mol/L), CT is always combined with other imaging modalities such as SPECT, PET to provide anatomical parameters for the biochemical and physiological findings.

Optical Imaging

Optical molecular imaging technology is an emerging technology, based on genomics, proteomics, and modern optical technology. At present, the most widely used optical molecular imaging modalities in vivo include bioluminescence imaging (BLI) and fluorescence imaging. As optical imaging is performed through the use of light, thus it is considered as relatively safe. And due to their advantages of high sensitivity and low cost, optical imaging plays a central role in the investigation of tumor occurrence, progressions and relevant drug development.

Ultrasound Molecular Imaging

With the use of ultrasound contrast agent, ultrasound imaging enables specific and sensitive depiction of molecular targets. Compared with other molecular imaging modalities, ultrasound molecular imaging has many advantages including good temporal resolution, quantitative data, real-time practice, noninvasiveness, relatively inexpensive cost, and no ionizing radiation. In addition, it is a unique modality in some sense that it can be employed for diagnostic imaging and as a therapeutic tool.

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Multimodality Imaging

Among all molecular imaging techniques, every molecular imaging technique has its advantages and disadvantages. No single one is perfect and enough to provide comprehensive information for disease diagnosis. In general, CT, MRI, and US are anatomic imaging methods but they have low sensitivity. Radionuclide imaging and optical imaging are functional imaging techniques, while they suffer from low resolution, which often lack structural parameter. The combination of different molecular imaging techniques, namely, multimodality imaging, can provide synergistic advantages over any modality alone and compensate for the disadvantages of each imaging system while taking advantage of their individual strengths, which has become the developmental trend of modern medical image now.

Imaging Agents

Molecular imaging depends greatly on the development of specific and sensitive imaging agents, which is a pivotal rate-limiting step in the development of molecular imaging. In a molecular imaging study, imaging agents are mainly used for interrogating or coupling back about a specific target of interest. They usually consist of signal component and targeting component. In recent years, the advancement of biochemistry has been achieved and the development of molecular imaging technologies has led to the production of a mass of molecular imaging agents.

The rapid expansion of molecular imaging application shows a promising prospect. Although overall the molecular imaging is still at the initial stage of development, we believe that within the support and cooperation from imaging experts and scholars, molecular imaging techniques would eventually realize clinical transformation.

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