Advances in Noninvasive Molecular Imaging Probes for Liver Fibrosis Diagnosis.

Liver fibrosis is a wound-healing response to chronic liver injury, which may lead to cirrhosis and cancer. Early-stage fibrosis is reversible, and it is difficult to precisely diagnose with conventional imaging modalities such as magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, and ultrasound imaging. In contrast, probe-assisted molecular imaging offers a promising noninvasive approach to visualize early fibrosis changes in vivo, thus facilitating early diagnosis and staging liver fibrosis, and even monitoring of the treatment response. Here, the most recent progress in molecular imaging technologies for liver fibrosis is updated. We start by illustrating pathogenesis for liver fibrosis, which includes capillarization of liver sinusoidal endothelial cells, cellular and molecular processes involved in inflammation and fibrogenesis, as well as processes of collagen synthesis, oxidation, and cross-linking. Furthermore, the biological targets used in molecular imaging of liver fibrosis are summarized, which are composed of receptors on hepatic stellate cells, macrophages, and even liver collagen. Notably, the focus is on insights into the advances in imaging modalities developed for liver fibrosis diagnosis and the update in the corresponding contrast agents. In addition, challenges and opportunities for future research and clinical translation of the molecular imaging modalities and the contrast agents are pointed out. We hope that this review would serve as a guide for scientists and students who are interested in liver fibrosis imaging and treatment, and as well expedite the translation of molecular imaging technologies from bench to bedside.

Recent advances in small molecular near-infrared fluorescence probes for a targeted diagnosis of the Alzheimer disease.

Nowadays, it is still quite challenging to achieve an early diagnosis of the Alzheimer disease (AD) in clinics. The burgeoning near-infrared fluorescence (NIRF) imaging fulfills the requirements for a precise diagnosis with good sensitivity and a high signal-to-background ratio and offers opportunities for the efficient AD diagnosis. As the pathogenesis of AD is quite complex, there is an ongoing exploration of advanced probes to specifically target AD biomarkers (e.g., amyloid-ß (Aß) plaques, neurofibrillary tangles, viscosity, peroxynitrite (ONOO-), reactive oxygen species, and methylglyoxal). To this end, a great number of small molecular fluorescent probes with good water solubility, blood-brain barrier crossing capability, and ease in tuning photophysical and biological properties have been studied for the AD diagnosis. Herein, we systematically update the progress of NIRF AD probes in the last three years. The special focus is on the mechanisms for the targeted diagnosis and the relationship between the structure and properties of the probes. Importantly, NIRF probes with complementary functions such as dual-responsiveness and multimodal imaging and even therapeutics are discussed. Moreover, the challenges and perspectives of the AD probes are briefly elucidated. We hope that this review provides guidance for researchers and expedites the preclinical and clinical study of the NIRF AD probes.

Recent development of contrast agents for magnetic resonance and multimodal imaging of glioblastoma.

Glioblastoma (GBM) as the most common primary malignant brain tumor exhibits a high incidence and degree of malignancy as well as poor prognosis. Due to the existence of formidable blood-brain barrier (BBB) and the aggressive growth and infiltrating nature of GBM, timely diagnosis and treatment of GBM is still very challenging. Among different imaging modalities, magnetic resonance imaging (MRI) with merits including high soft tissue resolution, non-invasiveness and non-limited penetration depth has become the preferred tool for GBM diagnosis. Furthermore, multimodal imaging with combination of MRI and other imaging modalities would not only synergistically integrate the pros, but also overcome the certain limitation in each imaging modality, offering more accurate morphological and pathophysiological information of brain tumors. Since contrast agents contribute to amplify imaging signal output for unambiguous pin-pointing of tumors, tremendous efforts have been devoted to advances of contrast agents for MRI and multimodal imaging. Herein, we put special focus on summary of the most recent advances of not only MRI contrast agents including iron oxide-, manganese (Mn)-, gadolinium (Gd)-, 19F- and copper (Cu)-incorporated nanoplatforms for GBM imaging, but also dual-modal or triple-modal nanoprobes. Furthermore, potential obstacles and perspectives for future research and clinical translation of these contrast agents are discussed. We hope this review provides insights for scientists and students with interest in this area.

Usefulness of diffusion derived vessel density computed from a simplified IVIM imaging protocol: An experimental study with rat biliary duct blockage induced liver fibrosis.

OBJECTIVES: Liver vessel density can be evaluated by DDVD (diffusion derived vessel density): DDVD(b0b1) = Sb0/ROIarea0 - Sb1/ROIarea1, where Sb0 and Sb1 refer to the liver signal when b is 0 or 1 s/mm2. Sb1 and ROIarea1 may be replaced by other b-values. With a rat biliary duct ligation (BDL) model, this study assesses the usefulness of liver DDVD computed from a simplified IVIM imaging protocol using b = 25 and b = 50 to replace b = 1 s/mm2, alone and in combination with other IVIM parameters. METHODS: Male Sprague-Dawley rats were used. The rat number was 5, 5, 5, and 3 respectively, for the timepoints of 7, 14, 21, 28 days post-BDL surgery. 12 rats had partial biliary duct recanalization performed after the rats had BDL for 7 days and then again followed-up for a mean of 14 days. Liver diffusion MRIs were acquired at 3.0 T with a b-value distribution of 0, 25, 50, 75, 100, 150, 300, 700, 1000 s/mm2. DDVDmean (control rats n = 6) was the mean of DDVD(b0b25) and DDVD(b0b50). IVIM fitting started from b = 0 s/mm2 with segmented fitting and a threshold b of 50 s/mm2 (n = 5 for control rats). Three 3-D spaces were constructed using a combination of the four diffusion parameters. RESULTS: The control rats and BDL rats (n = 18) had a liver DDVDmean of 84.0 ± 26.2 and 44.7 ± 14.4 au/pixel (p < 0.001). All 3-D spaces totally separated healthy livers and all fibrotic livers (n = 30, BDL rats and recanalization rats). The mean relative distance between healthy liver cluster and fibrotic liver cluster was 0.331 for PF, Dslow, and Dfast; 0.381 for PF, Dfast, and DDVDmean; and 0.384 for PF, Dslow, and DDVDmean. CONCLUSION: A combination of PF, Dslow, and Dfast allows total separation of healthy livers and fibrotic livers and the integration of DDVD improved the separation.