PET brain imaging in neurological disorders.

Brain disorders are a series of conditions with damage or loss of neurons, such as Parkinson's disease (PD), Alzheimer's disease (AD), or drug dependence. These individuals have gradual deterioration of cognitive, motor, and other central nervous system functions affected. This degenerative trajectory is intricately associated with dysregulations in neurotransmitter systems. Positron Emission Tomography (PET) imaging, employing radiopharmaceuticals and molecular imaging techniques, emerges as a crucial tool for detecting brain biomarkers. It offers invaluable insights for early diagnosis and distinguishing brain disorders. This article comprehensively reviews the application and progress of conventional and novel PET imaging agents in diagnosing brain disorders. Furthermore, it conducts a thorough analysis on merits and limitations. The article also provides a forward-looking perspective in the future development directions of PET imaging agents for diagnosing brain disorders and proposes potential innovative strategies. It aims to furnish clinicians and researchers with an all-encompassing overview of the latest advancements and forthcoming trends in the utilization of PET imaging for diagnosing brain disorders.

Improved Tau PET SUVR Quantification in 4-Repeat Tau Phenotypes with [18F]PI-2620.

We used a new data-driven methodology to identify a set of reference regions that enhanced the quantification of the SUV ratio of the second-generation tau tracer 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([18F]PI-2620) in a group of patients clinically diagnosed with 4-repeat tauopathy, specifically progressive supranuclear palsy or cortical basal syndrome. The study found that SUV ratios calculated using the identified reference regions (i.e., fusiform gyrus and crus-cerebellum) were significantly associated with symptom severity and disease duration. This establishes, for the first time to our knowledge, the suitability of [18F]PI-2620 for tracking disease progression in this 4-repeat disease population. This is an important step toward increased clinical utility, such as patient stratification and monitoring in disease-modifying treatment trials. Additionally, the applied methodology successfully optimized reference regions for automated detection of brain imaging tracers. This approach may also hold value for other brain imaging tracers.

Exosome-Coated Prussian Blue Nanoparticles for Specific Targeting and Treatment of Glioblastoma.

Glioblastoma is one of the most aggressive and invasive types of brain cancer with a 5-year survival rate of 6.8%. With limited options, patients often have poor quality of life and are moved to palliative care after diagnosis. As a result, there is an extreme need for a novel theranostic method that allows for early diagnosis and noninvasive treatment as current peptide-based delivery standards may have off-target effects. Prussian Blue nanoparticles (PBNPs) have recently been investigated as photoacoustic imaging (PAI) and photothermal ablation agents. However, due to their inability to cross the blood-brain barrier (BBB), their use in glioblastoma treatment is limited. By utilizing a hybrid, biomimetic nanoparticle composed of a PBNP interior and a U-87 cancer cell-derived exosome coating (Exo:PB), we show tumor-specific targeting within the brain and selective thermal therapy potential due to the strong photoconversion abilities. Particle characterization was carried out and showed a complete coating around the PBNPs that contains exosome markers. In vitro cellular uptake patterns are similar to native U-87 exosomes and when exposed to an 808 nm laser, show localized cell death within the specified region. After intravenous injection of Exo:PB into subcutaneously implanted glioblastoma mice, they have shown effective targeting and eradication of tumor volume compared to PEG-coated PBNPs (PEG:PB). Through systemic administration of Exo:PB particles into orthotopic glioblastoma-bearing mice, the PBNP signal was detected in the brain tumor region through PAI. It was seen that Exo:PB had preferential tumor accumulation with less off-targeting compared to the RGD:PB control. Ex vivo analysis validated specific targeting with a direct overlay of Exo:PB with the tumor by both H&E staining and Ki67 labeling. Overall, we have developed a novel biomimetic material that can naturally cross the BBB and act as a theranostic agent for systemic targeting of glioblastoma tissue and photothermal therapeutic effect.

Novel cutting edge nano-strategies to address old long-standing complications in cardiovascular diseases. A comprehensive review.

BACKGROUND: Cardiovascular diseases (CVD) impact a substantial portion of the global population and represent a significant threat to experiencing life-threatening outcomes, such as atherosclerosis, myocardial infarction, stroke and heart failure. Despite remarkable progress in pharmacology and medical interventions, CVD persists as a major public health concern, and now ranks as the primary global cause of death and the highest consumer of global budgets. Ongoing research endeavours persist in seeking novel therapeutic avenues and interventions to deepen our understanding of CVD, enhance prevention measures, and refine treatment strategies. METHODS: Nanotechnology applied to the development of new molecular probes with diagnostic and theranostic properties represents one of the greatest technological challenges in preclinical and clinical research. RESULTS: The application of nanotechnology in cardiovascular medicine holds great promise for advancing our understanding of CVDs and revolutionizing their diagnosis and treatment strategies, ultimately improving patient care and outcomes. In addition, the capacity of drug encapsulation in nanoparticles has significantly bolstered their biological safety, bioavailability and solubility. In combination with imaging technologies, molecular imaging has emerged as a pivotal therapeutic tool, offering insight into the molecular events underlying disease and facilitating targeted treatment approaches. CONCLUSION: Here, we present a comprehensive overview of the recent advancements in targeted nanoparticle approaches for diagnosing CVDs, encompassing molecular imaging techniques, underscoring the significant progress in theranostic, as a novel and promising therapeutic strategy.

An Update on MR Spectroscopy in Cancer Management: Advances in Instrumentation, Acquisition, and Analysis.

MR spectroscopy (MRS) is a noninvasive imaging method enabling chemical and molecular profiling of tissues in a localized, multiplexed, and nonionizing manner. As metabolic reprogramming is a hallmark of cancer, MRS provides valuable metabolic and molecular information for cancer diagnosis, prognosis, treatment monitoring, and patient management. This review provides an update on the use of MRS for clinical cancer management. The first section includes an overview of the principles of MRS, current methods, and conventional metabolites of interest. The remainder of the review is focused on three key areas: advances in instrumentation, specifically ultrahigh-field-strength MRI scanners and hybrid systems; emerging methods for acquisition, including deuterium imaging, hyperpolarized carbon 13 MRI and MRS, chemical exchange saturation transfer, diffusion-weighted MRS, MR fingerprinting, and fast acquisition; and analysis aided by artificial intelligence. The review concludes with future recommendations to facilitate routine use of MRS in cancer management. Keywords: MR Spectroscopy, Spectroscopic Imaging, Molecular Imaging in Oncology, Metabolic Reprogramming, Clinical Cancer Management © RSNA, 2024.

Nanobiotechnology augmented cancer stem cell guided management of cancer: liquid-biopsy, imaging, and treatment.

Cancer stem cells (CSCs) represent both a key driving force and therapeutic target of tumoral carcinogenesis, tumor evolution, progression, and recurrence. CSC-guided tumor diagnosis, treatment, and surveillance are strategically significant in improving cancer patients' overall survival. Due to the heterogeneity and plasticity of CSCs, high sensitivity, specificity, and outstanding targeting are demanded for CSC detection and targeting. Nanobiotechnologies, including biosensors, nano-probes, contrast enhancers, and drug delivery systems, share identical features required. Implementing these techniques may facilitate the overall performance of CSC detection and targeting. In this review, we focus on some of the most recent advances in how nanobiotechnologies leverage the characteristics of CSC to optimize cancer diagnosis and treatment in liquid biopsy, clinical imaging, and CSC-guided nano-treatment. Specifically, how nanobiotechnologies leverage the attributes of CSC to maximize the detection of circulating tumor DNA, circulating tumor cells, and exosomes, to improve positron emission computed tomography and magnetic resonance imaging, and to enhance the therapeutic effects of cytotoxic therapy, photodynamic therapy, immunotherapy therapy, and radioimmunotherapy are reviewed.

Behavioral and dysexecutive variant of Alzheimer's disease: Insights from structural and molecular imaging studies.

Frontal variant Alzheimer's disease (AD) manifests with either behavioral or dysexecutive syndromes. Recent efforts to gain a deeper understanding of this phenotype have led to a re-conceptualization of frontal AD. Behavioral (bAD) and dysexecutive (dAD) phenotypes could be considered subtypes, as suggested by both clinical and neuroimaging studies. In this review, we focused on imaging studies to highlight specific brain patterns in these two uncommon clinical AD phenotypes. Although studies did not compare directly these two variants, a common epicenter located in the frontal cortex could be inferred. On the contrary, 18F-FDG-PET findings suggested differing metabolic patterns, with bAD showing specific involvement of frontal regions and dAD exhibiting widespread alterations. Structural MRI findings confirmed this pattern, suggesting that degeneration might involve neural circuits associated with behavioral control in bAD and attentional networks in dAD. Furthermore, molecular imaging has identified different neocortical tau distribution in bAD and dAD patients compared to typical AD patients, although the distribution is remarkably heterogeneous. In contrast, Aß deposition patterns are less differentiated between these atypical variants and typical AD. Although preliminary, these findings underscore the complexity of AD frontal phenotypes and suggest that they represent distinct entities. Further research is essential to refine our understanding of the pathophysiological mechanisms in frontal AD.

An environmentally sensitive zinc-selective two-photon NIR fluorescent turn-on probe and zinc sensing in stroke.

A two-photon near infrared (NIR) fluorescence turn-on sensor with high selectivity and sensitivity for Zn2+ detection has been developed. This sensor exhibits a large Stokes' shift (∼300 nm) and can be excited from 900 to 1000 nm, with an emission wavelength of ∼785 nm, making it ideal for imaging in biological tissues. The sensor's high selectivity for Zn2+ over other structurally similar cations, such as Cd2+, makes it a promising tool for monitoring zinc ion levels in biological systems. Given the high concentration of zinc in thrombi, this sensor could provide a useful tool for in vivo thrombus imaging.

Mechanisms Leading to Increased Insulin-Stimulated Cerebral Glucose Uptake in Obesity and Insulin Resistance: A High-Fat Diet and Exercise Training Intervention PET Study with Rats (CROSRAT).

Recent studies have shown that obesity and insulin resistance are associated with increased insulin-stimulated glucose uptake (GU) in the brain. Thus, insulin sensitivity seems to work differently in the brain compared to the peripheral tissues like skeletal muscles, but the underlying mechanisms remain unknown. Regular exercise training improves skeletal muscle and whole-body insulin sensitivity. However, the effect of exercise on glucose metabolism in the brain and internal organs is less well understood. The CROSRAT study aims to investigate the effects of exercise training on brain glucose metabolism and inflammation in a high-fat diet-induced rat model of obesity and insulin resistance. Male Sprague Dawley rats (n = 144) are divided into nine study groups that undergo different dietary and/or exercise training interventions lasting 12 to 24 weeks. Insulin-stimulated GU from various tissues and brain inflammation are investigated using [18F]FDG-PET/CT and [11C]PK11195-PET/CT, respectively. In addition, peripheral tissue, brain, and fecal samples are collected to study the underlying mechanisms. The strength of this study design is that it allows examining the effects of both diet and exercise training on obesity-induced insulin resistance and inflammation. As the pathophysiological changes are studied simultaneously in many tissues and organs at several time points, the study provides insight into when and where these pathophysiological changes occur.

Enhancing surgical outcomes: accurate identification and removal of prostate cancer with B7-H3-targeted NIR-II molecular imaging.

PURPOSE: One of the main reasons for prostate cancer (PCa) recurrence is the difficulty in identifying and removing cancerous lesions during surgery. Accurately localizing and excising cancerous tissue remains a significant challenge. The second near-infrared window (NIR-II, 1000-1700 nm) fluorescence offers enhanced resolution, a high signal-to-noise ratio, and the potential for deeper tissue penetration. However, this technology is not currently employed for intraoperative imaging of PCa. This study aims to construct a new NIR-II probe targeting B7-H3 (AbB7-H3-800CW) for accurate intraoperative identification and resection of PCa. METHODS: Based on the differential expression of B7-H3 in PCa, we designed a novel imaging probe to accurately identify and guide the resection of preclinical PCa models and ex vivo human PCa tissues using NIR-II fluorescence imaging technology. RESULTS: Analyzing tissue samples from 60 clinical cases of PCa, along with benign prostatic hyperplasia and normal prostate tissue from 22 cases, we observed a significant difference in B7-H3 protein expression levels (P < 0.001). Subcutaneous and orthotopic mouse models of PCa were imaged using NIR-II fluorescence after AbB7-H3-800CW injection, showing promising results with successful tumor targeting and high-contrast images achieved within 24-48 h post-injection. The imaging also enabled the detection of occult PCa lesions approximately 1 mm in diameter. In addition, imaging analysis of human PCa and adjacent tissues using AbB7-H3-800CW incubation revealed that cancer tissues exhibited a significantly higher fluorescence intensity than adjacent tissues (P < 0.05), which was conducive to the evaluation of tumor resection margin in vitro. CONCLUSION: The findings revealed that B7-H3 was a compelling imaging target for PCa. The AbB7-H3-800CW molecular imaging probe is capable of accurately identifying PCa lesions and guiding their removal. This approach can potentially reduce the rate of surgical margins under NIR-II fluorescence guidance.

Alterations in lipid metabolism accompanied by changes in protein and carotenoid content as spectroscopic markers of human T cell activation.

This work aims to understand better the mechanism of cellular processes accompanying the activation of human T cells and to develop a novel, fast, label-free approach to identify molecular biomarkers for this process. Non-activated T-cell activation is a key method in cancer immunotherapy and involves the isolation of T-cells from a patient to perform a specific genetic modification. The standard methodology for confirming the activation state of T cells is based on flow cytometry, antibodies, and target antigens that provide high specificity detection but may show background staining or specific secondary antibody reactions. Here, we evaluated the potential of Raman-based molecular imaging in differentiating non-activated and activated human T cells. Confocal Raman microscopy was performed on activated T cells using chemometrics to obtain comprehensive molecular information, while Stimulated Raman Scattering imaging was used to quickly provide high-resolution images of selected cellular components of activated and non-activated cells. For the first time, carotenoids, lipids, and proteins were shown to be important biomarkers of T-cell activation. We found that T-cell activation was accompanied by lipid accumulation and loss of carotenoid content. Our findings on the biochemical, morphological, and structural changes associated with activated mature T cells provide insights into the molecular changes that occur during therapeutic manipulation of the immune response. The methodology for identifying activated T cells is based on a novel imaging method and supervised and unsupervised chemometrics. It unambiguously identifies specific and unique molecular changes without the need for staining, fixation, or any other sample preparation.

Recent advances in the development of 225Ac- and 211At-labeled radioligands for radiotheranostics.

Radiotheranostics utilizes a set of radioligands incorporating diagnostic or therapeutic radionuclides to achieve both diagnosis and therapy. Imaging probes using diagnostic radionuclides have been used for systemic cancer imaging. Integration of therapeutic radionuclides into the imaging probes serves as potent agents for radionuclide therapy. Among them, targeted alpha therapy (TAT) is a promising next-generation cancer therapy. The α-particles emitted by the radioligands used in TAT result in a high linear energy transfer over a short range, inducing substantial damage to nearby cells surrounding the binding site. Therefore, the key to successful cancer treatment with minimal side effects by TAT depends on the selective delivery of radioligands to their targets. Recently, TAT agents targeting biomolecules highly expressed in various cancer cells, such as sodium/iodide symporter, norepinephrine transporter, somatostatin receptor, αvß3 integrin, prostate-specific membrane antigen, fibroblast-activation protein, and human epidermal growth factor receptor 2 have been developed and have made remarkable progress toward clinical application. In this review, we focus on two radionuclides, 225Ac and 211At, which are expected to have a wide range of applications in TAT. We also introduce recent fundamental and clinical studies of radiopharmaceuticals labeled with these radionuclides.

Molecular imaging reveals the heterogeneous progression of tumor cells and tumor stroma: a practice of FDG PET and FAPI PET in diagnosing PSMA-negative bone metastases of progressive prostate cancer.

Tumors are often with complex and heterogeneous biological processes, such as glycometabolism and fibrosis, which are the main biochemical pathways that determine therapeutic effects. Specifically, this study aims to assess the diagnosing performance of 18F-FDG and 68Ga-FAPI-04 PET for different stages of progressive bone metastases with PSMA-negative pathology. Bone metastatic mouse model of prostate cancer was constructed via intra-bone injection of PSMA-negative prostate cancer PC3 cells. Cellular uptakes of 18F-FDG and 68Ga-FAPI-04 were separately performed on PC3, NIH-3T3 (FAP-positive) and a mixture. 68Ga-PSMA-11, 18F-FDG and 68Ga-FAPI-04 PET/CT imaging were performed at 2, 4 weeks after tumor cell transplantation. Furthermore, PSMA and FAP expression in bone metastases were assessed by immunohistochemistry, and then compared with the imageological findings. On the cellular level, the independent tracer uptake on the basis of glycometabolism and fibrosis was observed. For animal imaging, 68Ga-PSMA-11 imaging showed weak or absent tracer uptake in PSMA-negative bone metastatic lesions. In contrast, 68Ga-FAPI-04 PET of bone metastases had a higher uptake and tumor-to-muscle (T/M) ratio than 18F-FDG PET that was relative steady during the observation, but T/M ratio of fibrosis gradually decreased with increasing tumor growth, which ranged from 5.11 ± 1.26 at 2 weeks to 3.54 ± 0.23 at 4 weeks, revealing the delayed formation of tumor stroma in rapid proliferation. In addition, PET imaging results were corroborated by immunohistochemical assessment. In conclusion, molecular imaging approach revealed the heterogeneous progression of tumor cells and tumor stroma of bone metastasis of prostate cancer, and further confirming the necessity of multi-molecular imaging in cancer imaging.

Molecular Engineering of Activatable NIR-II Hemicyanine Reporters for Early Diagnosis and Prognostic Assessment of Inflammatory Bowel Disease.

Molecular imaging in the second near-infrared window (NIR-II) provides high-fidelity visualization of biopathological events in deep tissue. However, most NIR-II probes produce "always-on" output and demonstrate poor signal specificity toward biomarkers. Herein, we report a series of hemicyanine reporters (HBCs) with tunable emission to NIR-II window (715-1188 nm) and structurally amenable to constructing activatable probes. Such manipulation of emission wavelengths relies on rational molecular engineering by integrating benz[c,d]indolium, benzo[b]xanthonium, and thiophene moieties to a conventional hemicyanine skeleton. In particular, HBC4 and HBC5 possess bright and record long emission over 1050 nm, enabling improved tissue penetration depth and superior signal to background ratio for intestinal tract mapping than NIR-I fluorophore HC1. An activatable inflammatory reporter (AIR-PE) is further constructed for pH-triggered site-specific release in colon. Due to minimized background interference, oral gavage of AIR-PE allows clear delineation of irritated intestines and assessment of therapeutic responses in a mouse model of inflammatory bowel disease (IBD) through real-time NIRF-II imaging. Benefiting from its high fecal clearance efficiency (>90%), AIR-PE can also detect IBD and evaluate the effectiveness of colitis treatments via in vitro optical fecalysis, which outperforms typical clinical assays including fecal occult blood testing and histological examination. This study thus presents NIR-II molecular scaffolds that are not only applicable to developing versatile activatable probes for early diagnosis and prognostic monitoring of deeply seated diseases but also hold promise for future clinical translations.

Molecular Imaging of Diffuse Cardiac Fibrosis with a Radiotracer That Targets Proteolyzed Collagen IV.

Purpose To develop an approach for in vivo detection of interstitial cardiac fibrosis using PET with a peptide tracer targeting proteolyzed collagen IV (T-peptide). Materials and Methods T-peptide was conjugated to the copper chelator MeCOSar (chemical name, 5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid) and radiolabeled with copper 64 (64Cu). PET/CT scans were acquired following intravenous delivery of 64Cu-T-peptide-MeCOSar (0.25 mg/kg; 18 MBq ± 2.7 [SD]) to male transgenic mice overexpressing ß2-adrenergic receptors with intermediate (7 months of age; n = 4 per group) to severe (10 months of age; n = 11 per group) cardiac fibrosis and their wild-type controls. PET scans were also performed following coadministration of the radiolabeled probe with nonlabeled T-peptide in excess to confirm binding specificity. PET data were analyzed by t tests for static scans and analysis of variance tests (one- or two-way) for dynamic scans. Results PET/CT scans revealed significantly elevated (2.24-4.26-fold; P < .05) 64Cu-T-peptide-MeCOSar binding in the fibrotic hearts of aged transgenic ß2-adrenergic receptor mice across the entire 45-minute acquisition period compared with healthy controls. The cardiac tracer accumulation and presence of diffuse cardiac fibrosis in older animals were confirmed by gamma counting (P < .05) and histologic evaluation, respectively. Coadministration of a nonradiolabeled probe in excess abolished the elevated radiotracer binding in the aged transgenic hearts. Importantly, PET tracer accumulation was also detected in younger (7 months of age) transgenic mice with intermediate cardiac fibrosis, although this was only apparent from 20 minutes following injection (1.6-2.2-fold binding increase; P < .05). Conclusion The T-peptide PET tracer targeting proteolyzed collagen IV provided a sensitive and specific approach of detecting diffuse cardiac fibrosis at varying degrees of severity in a transgenic mouse model. Keywords: Diffuse Cardiac Fibrosis, Molecular Peptide Probe, Molecular Imaging, PET/CT © RSNA, 2024.

Saliency enhancement method for photoacoustic molecular imaging based on Grüneisen relaxation nonlinear effect.

Photoacoustic molecular imaging technology has a wide range of applications in biomedical research. In practical scenarios, both the probes and blood generate signals, resulting in the saliency of the probes in the blood environment being diminished, impacting imaging quality. Although several methods have been proposed for saliency enhancement, they inevitably suffer from moderate generality and detection speed. The Grüneisen relaxation (GR) nonlinear effect offers an alternative for enhancing saliency and can improve generality and speed. In this article, the excitation and detection efficiencies are optimized to enhance the GR signal amplitude. Experimental studies show that the saliency of the probe is enhanced. Moreover, the issue of signal aliasing is studied to ensure the accuracy of enhancement results in the tissues. In a word, the feasibility of the GR-based imaging method in saliency enhancement is successfully demonstrated in the study, showing the superiorities of good generality and detection speed.

H-ferritin-nanocaged gadolinium nanoparticles for ultra-sensitive MR molecular imaging.

Rationale: Magnetic resonance imaging (MRI) is a powerful diagnostic technology by providing high-resolution imaging. Although MRI is sufficiently valued in its resolving morphology, it has poor sensitivity for tracking biomarkers. Therefore, contrast agents are often used to improve MRI diagnostic sensitivity. However, the clinically used Gd chelates are limited in improving MRI sensitivity owing to their low relaxivity. The objective of this study is to develop a novel contrast agent to achieve a highly sensitive tracking of biomarkers in vivo. Methods: A Gd-based nanoprobe composed of a gadolinium nanoparticle encapsulated within a human H-ferritin nanocage (Gd-HFn) has been developed. The specificity and sensitivity of Gd-HFn were evaluated in vivo in tumor-bearing mice and apolipoprotein E-deficient mice (Apoe-/-) by MRI. Results: The Gd-HFn probe shows extremely high relaxivity values (r1 = 549 s-1mM-1, r2 = 1555 s-1mM-1 under a 1.5-T magnetic field; and r1 = 428 s-1mM-1 and r2 = 1286 s-1mM-1 under a 3.0-T magnetic field), which is 175-fold higher than that of the clinically standard Dotarem (Gd-DOTA, r1 =3.13 s-1mM-1) under a 1.5-T magnetic field, and 150-fold higher under a 3.0-T magnetic field. Owing to the substantially enhanced relaxivity values, Gd-HFn achieved a highly sensitive tracking for the tumor targeting receptor of TfR1 and enabled the in vivo MRI visualization of tumors approaching the angiogenic switch. Conclusions: The developed Gd-HFn contrast agent makes MRI a more powerful tool by simultaneously providing functional and morphological imaging information, which paves the way for a new perspective in molecular imaging.

Evaluation of Oil-Absorbing Film for Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging (IDESI-MSI) on Biological Samples.

Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging (IDESI-MSI) has proven to be a robust and reliable tool for chemically imaging biological samples such as fungi, animal tissues, and plants, but the choice of the imprint substrate is crucial. It must effectively transfer maximum amounts of species from the sample while preserving the original spatial distribution of detected molecules. In this study, we explored the potential of utilizing an oil-absorbing film, known for its soft nature and excellent lipophilicity, as an imprint substrate for IDESI-MSI on biological samples. To assess the transfer efficiency of the amounts of molecules and molecular patterns, we conducted experiments using mouse brain tissue. The result shows that more than 90% of the analytes can be transferred to the oil-absorbing film from the original tissue. A comparison of IDESI-MSI results between the oil-absorbing film and the original tissue demonstrates the material's capability to transfer most molecules from the original tissue and retain images of different analytes with high spatial fidelity. We extended our investigation to plant imaging, where we applied IDESI-MSI to a cross-section of okra. The oil-absorbing film exhibited promise in this context as well. These findings suggest that IDESI-MSI utilizing the oil-absorbing film holds potential across various research fields, including biological metabolism, chemistry, and clinical research, making this technique widely applicable.

Longitudinal Magnetic Resonance Imaging Tracking of Transplanted Neural Progenitor Cells in the Spinal Cord Utilizing the Bright-Ferritin Mechanism.

Human neural progenitor cells (hNPCs) hold promise for treating spinal cord injury. Studies to date have focused on improving their regenerative potential and therapeutic effect. Equally important is ensuring successful delivery and engraftment of hNPCs at the injury site. Unfortunately, no current imaging solution for cell tracking is compatible with long-term monitoring in vivo. The objective of this study was to apply a novel bright-ferritin magnetic resonance imaging (MRI) mechanism to track hNPC transplants longitudinally and on demand in the rat spinal cord. We genetically modified hNPCs to stably overexpress human ferritin. Ferritin-overexpressing (FT) hNPCs labeled with 0.2 mM manganese provided significant T1-induced bright contrast on in vitro MRI, with no adverse effect on cell viability, morphology, proliferation, and differentiation. In vivo, 2 M cells were injected into the cervical spinal cord of Rowett nude rats. MRI employed T1-weighted acquisitions and T1 mapping on a 3 T scanner. Conventional short-term cell tracking was performed using exogenous Mn labeling prior to cell transplantation, which displayed transient bright contrast on MRI 1 day after cell transplantation and disappeared after 1 week. In contrast, long-term cell tracking using bright-ferritin allowed on-demand signal recall upon Mn supplementation and precise visualization of the surviving hNPC graft. In fact, this new cell tracking technology identified 7 weeks post-transplantation as the timepoint by which substantial hNPC integration occurred. Spatial distribution of hNPCs on MRI matched that on histology. In summary, bright-ferritin provides the first demonstration of long-term, on-demand, high-resolution, and specific tracking of hNPCs in the rat spinal cord.