Figure S8. Quantification of manganese content in the PANC1 tumor 60 minutes post-injection of MnL3. MnL3 exhibited significantly higher tumor uptake in PANC1 tumors treated with one dose of FOLFIRINOX compared to the untreated mice (0.1 mmol/kg, i.v., 60 min p.i., n = 4 for each group, Student’s t-test, two-tailed, *P<0.05).

Figure S10. Quantification of manganese content in the 1319 tumor 60 minutes post-injection of MnL3. After randomly assigning 1319 mice to the vehicle or FOLFIRINOX group, MnL3 showed equivalent tumor uptake (0.1 mmol/kg, i.v., 60 min p.i., n = 5 for each group, Student’s t-test. ns: not significant).

Figure S5. Immediate dynamic contrast enhanced (DCE) MRI in PDAC6 tumor with MnL4 performed before, at 3 days (1 dose FOLFIRNOX), or at 7 days (2 doses FOLFIRINOX) after the initiation of FOLFIRINOX treatment. Time course of change in normalized signal intensity acquired from DCE images with MnL4 as the probe (0.1 mmol/kg, i.v., n = 4 for each group, data shown as mean value with 95% simultaneous confidence bands as shaded regions). Data are superimposable at each time point measured, indicating no changes in tumor permeability or extracellular volume with FOLFIRINOX treatment.

Figure S4. The PDAC6 tumor percentage change of normalized signal intensity (%nSI, normalized to an adjacent phantom) at 30 min p.i. of probe (n = 4 for each group). One-way ANOVA with Tukey’s post hoc test, *P<0.05, **P < 0.01, ns, not significant.

Figure S7. MnL3 molecular MRI of PANC1 tumor-bearing mice before administration of vehicle or FOLFIRINOX. After randomly assigning PANC1 mice to FOLFIRINOX or vehicle group, MnL3 molecular MRI (0.1 mmol/kg, i.v., 60 min p.i.) showed equivalent tumor enhancement before administration of vehicle or FOLFIRINOX. (n = 8 for each group, Student’s t-test, two-tailed, ns, not significant.).

Figure S2. Mass spectra of MnL4 before and after incubation with butyraldehyde. (A) MS spectrum of MnL4. [M + H]+ calcd for [C25H39MnN6O7], 590.2; found 590.0. (B) MnL4 did not react with butyraldehyde at pH 7.4 (PBS). [M + H]+ calcd for [C25H39MnN6O7], 590.2; found 590.0). (C) MnL4 did not react with butyraldehyde at pH 6.5 (PBS). [M + H]+ calcd for [C25H39MnN6O7], 590.2; found 590.0).

This study introduces a domain-conditioned and temporally guided diffusion framework for accelerated dynamic MRI reconstruction, in which the reverse diffusion process is explicitly guided to model spatiotemporal structure in time-resolved data. The framework integrates temporal information from time-resolved dimensions, allowing for the concurrent capture of intraframe spatial features and interframe temporal dynamics in diffusion modeling. Meanwhile, it employs additional spatiotemporal and self-consistent frequency-temporal priors to guide the diffusion process, ensuring precise temporal alignment and enhancing fine image detail recovery. To facilitate a smooth diffusion process, the nonlinear conjugate gradient algorithm is utilized during the reverse diffusion steps. The proposed model was tested on two types of MRI data: Cartesian-acquired multicoil cardiac MRI and golden-angle-radial-acquired multicoil free-breathing lung MRI, across various undersampling rates. It achieved high-quality reconstructions, demonstrating improved temporal alignment and structural recovery compared with other competitive reconstruction methods, both qualitatively and quantitatively. This diffusion framework exhibited robust performance in handling both Cartesian and non-Cartesian acquisitions, effectively reconstructing dynamic datasets in cardiac and lung MRI under different imaging conditions.

Chronic cardiopulmonary, metabolic, and renal diseases represent an immense global health burden, yet access to organ-specific diagnostics remains limited outside of hospitals. Most clinical assessments rely on imaging or laboratory testing that is costly, infrastructure-dependent, and impractical for large-scale or longitudinal monitoring in community settings. Here, we introduce VitoCheck, a compact, user-friendly electrical impedance tomography (EIT) platform that provides non-invasive evaluation of lung, heart, liver, and kidney function within minutes. We first demonstrate system stability, spatial specificity, and spectral sensitivity through controlled phantom studies. We then validate VitoCheck in clinical cohorts by demonstrating accurate EIT-based predictions of standard diagnostic metrics, including spirometry-derived forced expiratory volumes, echocardiography-derived ejection fraction, ultrasound-derived liver fat scores, and blood serum-derived kidney filtration. User feedback further highlights the rapid scan workflow that supports deployment by non-specialists in decentralized environments. By combining portable and easy-to-use hardware with quantitative organ health analytics, VitoCheck enables scalable screening and proactive disease management for use in remote and out-of-clinic care. ### Competing Interest Statement RWC is a co-founder, shareholder and employee of E-SENSE Innovation & Technology Ltd., Hong Kong, China. BJE is a contractor and shareholder of E-SENSE Innovation & Technology Ltd., Hong Kong, China. JHWL is a consultant of E-SENSE Innovation & Technology Ltd., Hong Kong, China. The other authors do not have any conflict of interest. ### Funding Statement The work was funded in part by the Mitzi, Lee Leung Yin Ping Charitable Foundation, E-SENSE Innovation & Technology internal funds, and to a lesser extent the Hong Kong Innovation Technology Fund InnoHK Project at Centre for Cerebro-Cardiovascular Health Engineering ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Informed Consent was provided to recruited participants across four studies targeting kidney, lung, heart, and liver function. All protocols were approved by the Institutional Review Board of The University of Hong Kong (lung: UW-21-579, kidney: UW-21-579, liver: UW-21-265) or the Hospital Authority Hong Kong West Cluster (heart: HKSTP-CREC 2024-023) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. The raw EIT data can be provided by RWC pending scientific review and a completed material transfer agreement. Requests for the raw EIT data should be submitted to Russell{at}esense-inno.tech. Sample datasets generated and analyzed during the current study will be made available in a public Zenodo/Dryad repository upon publication. Custom code used for EIT data analysis will be made available in a public GitHub repository upon publication.

Figure S1. Mass spectra of MnL3 solutions before and after reaction with butyraldehyde. (A) MS spectrum of MnL3. [M + H]+ calcd for [C20H32MnN7O5], 505.2; found 505.0. (B) MS spectrum of the reaction product between MnL3 and butyraldehyde at pH 7.4 (PBS). [M + H]+ calcd for [C24H38MnN7O5], 559.2; found 559.5. (C) MS spectrum of the reaction product between MnL3 and butyraldehyde at pH 6.5(PBS).

Figure S6. Quantification of manganese content in the PDAC6 tumor 60 minutes post-injection of MnL3. MnL3 (0.1 mmol/kg, i.v., 60 min p.i.) exhibited significantly higher tumor uptake at 3 days (P = 0.05) and 7 days (P = 0.04) after initiation of FOLFIRINOX treatment compared to the untreated tumor (One-way ANOVA with Tukey’s post hoc test, *P<0.05, ns, not significant. n = 6 for day 0 and day 3, n = 5 for day 7).

Figure S9. MnL3 molecular MRI of 1319 tumor-bearing mice before administration of vehicle or FOLFIRINOX. After randomly assigning 1319 mice to the vehicle or FOLFIRINOX group, MnL3 molecular MRI showed equivalent tumor enhancement before administration of vehicle or FOLFIRINOX. ( n = 4 for each group, Student’s t-test. ns: not significant).

OBJECTIVES:Development of molecular therapies for liver fibrosis is slowed by a lack of noninvasive methods addressing questions of target expression, target engagement, and treatment response. Integrin α v β 6 is a biomarker of liver fibrosis that is upregulated in livers of patients with primary sclerosing cholangitis. It activates latent TGF-β and plays a critical role in regulating extracellular matrix expression, especially collagen. In this study, our aim was to use combined α v β 6 integrin-targeted positron emission tomography (PET) and collagen-specific magnetic resonance imaging (MRI) to measure target expression/engagement and liver fibrosis reduction with a α v β 6 integrin inhibitor. MATERIALS AND METHODS:We conducted a treatment study in bile duct-ligated (BDL) rats using a small molecule inhibitor to α v β 6 /α v β 1 . 68 Ga-DOTA-R01-MG, an α v β 6 -specific PET probe, was used to noninvasively measure α v β 6 expression and target engagement in the liver. CM-101, a type I collagen MRI probe, was used to quantify fibrosis. RESULTS:68 Ga-DOTA-R01-MG PET showed 3-fold higher liver uptake in BDL rats compared with sham rats at 17 days after surgery. Pretreatment with high dose α v β 6 /α v β 1 inhibitor 1 hour before imaging significantly decreased liver PET uptake in BDL rats (31%, P  = 0.012). Two weeks of daily dosing with an α v β 6 /α v β 1 inhibitor attenuated α v β 6 expression in BDL rat liver as assessed by α v β 6 PET (0.27 ± 0.07 percent injected dose [%ID]/mL compared with 0.40 ± 0.09 %ID/mL in vehicle-treated group, P  = 0.014) and reduced liver fibrosis as assessed by collagen MRI (liver relaxation rate change ΔR 1  = 0.14 ± 0.11 vs 0.36 ± 0.06, P  = 0.0037). Imaging findings were confirmed by histology (collagen proportionate area 10.7 ± 2.8% vs 22.5 ± 6.1%, P  < 0.001). CONCLUSIONS:A single imaging protocol combining molecular MRI and PET can be used to effectively monitor integrin inhibitor treatment by measuring target expression/engagement and treatment outcomes. Multimodality molecular imaging may be valuable in accelerating drug development in molecular therapies for liver fibrosis.

Supplementary method, supplementary figure legends, and references.

Figure S3. Dynamic tumor %nSI in PDAC6 tumor-bearing mice after injection of MnL3 or MnL4. MnL4 (0.1 mmol/kg, i.v.) only produced transient signal enhancement after injection, while MnL3 (0.1 mmol/kg, i.v.) produced persistent and higher signal enhancement in tumors. (n = 4 for each group).

Fibrosing lung diseases affect over 160,000 individuals in the United States alone and can carry a prognosis that is worse than many cancers. Antifibrotic treatments modify only the rate of fibrosis progression, and more effective therapies are urgently needed. Molecular imaging enables visualization of disease pathogenesis in progress. It provides a noninvasive means to monitor and quantify dysregulated molecular fibrotic pathways and shows great promise in aiding the diagnosis and disease activity monitoring of pulmonary fibrosis. Here, we review molecular imaging probes under development for use in pulmonary fibrosis. We provide our opinion on current challenges in translating preclinical molecular imaging probes into clinical successes, as well as future directions for expanding their use in drug development.

Purpose: To propose a domain-conditioned and temporal-guided diffusion modeling method, termed dynamic Diffusion Modeling (dDiMo), for accelerated dynamic MRI reconstruction, enabling diffusion process to characterize spatiotemporal information for time-resolved multi-coil Cartesian and non-Cartesian data. Methods: The dDiMo framework integrates temporal information from time-resolved dimensions, allowing for the concurrent capture of intra-frame spatial features and inter-frame temporal dynamics in diffusion modeling. It employs additional spatiotemporal (x-t) and self-consistent frequency-temporal (k-t) priors to guide the diffusion process. This approach ensures precise temporal alignment and enhances the recovery of fine image details. To facilitate a smooth diffusion process, the nonlinear conjugate gradient algorithm is utilized during the reverse diffusion steps. The proposed model was tested on two types of MRI data: Cartesian-acquired multi-coil cardiac MRI and Golden-Angle-Radial-acquired multi-coil free-breathing lung MRI, across various undersampling rates. Results: dDiMo achieved high-quality reconstructions at various acceleration factors, demonstrating improved temporal alignment and structural recovery compared to other competitive reconstruction methods, both qualitatively and quantitatively. This proposed diffusion framework exhibited robust performance in handling both Cartesian and non-Cartesian acquisitions, effectively reconstructing dynamic datasets in cardiac and lung MRI under different imaging conditions. Conclusion: This study introduces a novel diffusion modeling method for dynamic MRI reconstruction.

Patient outcomes in metabolic dysfunction-associated steatohepatitis (MASH) are associated with the presence and stage of liver fibrosis. Activated hepatic stellate cells are a key mediator of MASH fibrogenesis and show increased expression of integrin αvβ3, making it a promising target for imaging and treatment of liver fibrosis. The ability to noninvasively measure target engagement of integrin inhibitors is key to understanding their chances of success in clinical development. Methods: Target engagement was assessed using PET imaging of an arginine-glycine-aspartic acid (RGD)-based integrin-binding tracer 18F-FPP-RGD2 Mice were fed a choline-deficient, ʟ-amino acid-defined, high-fat diet (CDAHFD) or control diet for 2, 6, 10, or 14 wk to induce fibrosis (n = 6/time point). PET was conducted on subsequent days without and with an oral dose of integrin αvβ3 antagonist IDL-2965 (10 mg/kg). The antifibrotic activity was evaluated in mice fed CDAHFD for 12 wk and treated with daily oral IDL-2965 (10 mg/kg) or vehicle in weeks 5-12. Integrin β3 expression was evaluated in liver biopsies from patients with varying degrees of fibrosis. Results: Significantly higher liver uptake of the integrin-binding PET tracer was found in MASH mice than in age-matched controls and increased with the duration of CDAHFD up to 10 wk. At each stage of fibrotic progression, a single oral dose of IDL-2965 significantly reduced hepatic 18F-FPP-RGD2 uptake, consistent with strong IDL-2965 target engagement. In a separate study, therapeutic administration of IDL-2965 significantly reduced multiple measures of CDAHFD-induced liver fibrosis, including histologic fibrosis scores, Sirius Red-stained area, hydroxyproline content, Col1α1 messenger RNA expression, and plasma cytokeratin-18. In human liver biopsies, integrin β3 expression increased with increasing fibrosis score. Conclusion: Increased expression of integrin αvβ3 and strong target engagement by IDL-2965 in the CDAHFD-induced MASH model can be detected in vivo using the integrin-binding PET tracer 18F-FPP-RGD2 Consistent with strong target engagement, therapeutic administration of IDL-2965 significantly reduced multiple measures of CDAHFD-induced hepatic fibrosis.

Liver fibrosis is a common pathway shared by all forms of progressive chronic liver disease. There is an unmet clinical need for noninvasive imaging tools to diagnose and stage fibrosis, which presently relies heavily on percutaneous liver biopsy. Here we explored the feasibility of using a novel type I collagen-targeted manganese (Mn)-based MRI probe, Mn-CBP20, for liver fibrosis imaging. In vitro characterization of Mn-CBP20 demonstrated its high binding affinity for human collagen (Kd = 9.6 µM), high T1-relaxivity (48.9 mM-1s-1 at 1.4T and 27°C), and kinetic inertness to Mn release under forcing conditions. We demonstrated MRI using Mn-CBP20 performs comparably to previously reported gadolinium-based type I collagen-targeted probe EP-3533 in a mouse model of carbon tetrachloride-induced liver fibrosis, and further demonstrate efficacy to detect fibrosis in a diet-induced mouse model of metabolically-associated steatohepatitis. Biodistribution studies using the Mn-CBP20 radio-labeled with the positron-emitting 52Mn isotope demonstrate efficient clearance of Mn-CBP20 primarily via renal excretion. Mn-CBP20 represents a promising candidate that merits further evaluation and development for molecular imaging of liver fibrosis.

Background Aging‐associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)–magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model. Methods and Results Left ventricular dysfunction was induced by transverse aortic constriction (TAC) in 6‐month‐old senescence‐accelerated prone mice, a subset of mice that received sham surgery. Three weeks after surgery, mice underwent simultaneous PET‐MRI at 4.7 T. Collagen‐targeted PET and fibrogenesis magnetic resonance (MR) probes were intravenously administered. PET signal was computed as myocardium‐ or lung‐to‐muscle ratio. Percent signal intensity increase and Δ lung‐to‐muscle ratio were computed from the pre‐/postinjection magnetic resonance images. Elevated allysine in the heart ( P =0.02) and lungs ( P =0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase ( P <0.0001) and Δlung‐to‐muscle ratio ( P <0.0001). Hydroxyproline in the heart ( P <0.0001) and lungs ( P <0.01) were elevated in TAC mice, which corresponded to an increase in heart (myocardium‐to‐muscle ratio, P =0.02) and lung (lung‐to‐muscle ratio, P <0.001) PET measurements. Pressure‐volume loop and echocardiography demonstrated adverse left ventricular remodeling, function, and increased right ventricular systolic pressure in TAC mice. Conclusions Administration of collagen‐targeted PET and allysine‐targeted MR probes led to elevated PET–magnetic resonance imaging signals in the myocardium and lungs of TAC mice. The study demonstrates the potential to detect fibrosis and fibrogenesis in cardiopulmonary disease through a dual molecular PET–magnetic resonance imaging protocol.

Purpose: Radiation-induced lung injury (RILI) is a progressive in fl ammatory process seen after irradiation for lung cancer. The disease can be insidious, often characterized by acute pneumonitis followed by chronic fi brosis with signi fi cant associated morbidity. No therapies are approved for RILI, and accurate disease quanti fi cation is a major barrier to improved management. Here, we sought to noninvasively quantify RILI using a molecular imaging probe that speci fi cally targets type 1 collagen mouse models and patients with con fi rmed RILI. Methods and Materials: Using a murine model of lung radiation, mice were imaged with EP-3533, a type 1 collagen probe, to characterize the development of RILI and to assess disease mitigation after losartan treatment. The human analog probe 68 Ga-CBP8, targeting type 1 collagen, was tested on excised human lung tissue containing RILI and was quanti fi ed via radiography. 68 Ga-CBP8 positron emission tomography was used to assess RILI in vivo in 6 human subjects. Results: Murine models demonstrated that probe signal correlated with progressive RILI severity over 6 months. The probe was sensitive to mitigation of RILI by losartan. Excised human lung tissue with RILI had increased binding versus unirradiated control tissue, and 68 Ga-CBP8 uptake correlated with collagen proportional area. Human imaging revealed signi fi 68 Ga-CBP8 uptake in areas of RILI and minimal background uptake. Conclusions: These fi ndings support the ability of a molecular imaging probe targeted at type 1 collagen to detect RILI in pre clinical models and human disease, suggesting a role for targeted molecular imaging of collagen in the assessment of RILI. 2023 Elsevier Inc. All rights reserved.