Stroke, Volume 56, Issue Suppl_1, Page AWP204-AWP204, February 1, 2025. Introduction:Prolonged venous outflow (PVT+) is a surrogate marker for venous outflow. The PVT is defined as the presence or absence of time-to-maximum >= 10 seconds timing in either the superior saggital sinus or torcula on visual time-to-maximum maps from perfusion imaging. This novel metric has been shown to be associated with higher odds of mortality and lower liklihood of functional recovery, despite successful reperfusion with mechanical thrombectomy. The study aims to assess the relationship between PVT and length of hospitalization. We hypotheisze that PVT+ will be associated with longer lengths of stay.Methods:Acute large vessel occlusion ischemic stroke patients successfully reperfused with thrombectomy between 01/2017-09/2022 were retrospectively reviewed. Primary outcome was length of hospitalization. Multivariable linear regressions were performed for the outcome of length of stay.Results:Of 109 patients, the median age was 71 (IQR 62-80) years. PVT+ patients had significantly longer lengths of stay than PVT- patients (9 days (IQR 6-18) versus 6 days (IQR 4-12), p=0.03). In multivariable regressions adjusting for other clinical covariables, PVT+ was significantly associated with two additional days of hospitalization compared to PVT- patients (p=0.03).Conclusion:Despite successful reperfusion, PVT+ was associated with two additional days of hospitalization on average comapred to PVT- patients. PVT is a simple, qualitative metric that demonstrates robustness in correlations with a range of short and long term clinical outcomes, and thus this novel surrogate of venous outflow may be informative for clinical practice.
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Abstract TP36: Parvalbumin Inhibitory Interneurons in Post-Stroke Recovery: Insights from Imaging and Optogenetics
Stroke, Volume 56, Issue Suppl_1, Page ATP36-ATP36, February 1, 2025. Stroke, the leading cause of adult disability, necessitates new therapeutic strategies informed by a deeper understanding of brain repair mechanisms. This pilot study investigates the role of parvalbumin inhibitory interneurons (PV-INs) in post-stroke recovery using wide-field optical imaging (WFOI) and optogenetics. PV-INs, the largest subclass of GABAergic interneurons, are crucial in regulating cortical excitability and mediating activity-dependent plasticity. However, their specific function in stroke recovery remains unclear.Here we use 5 aged mice expressing Channelrhodopsin (ChR2) in PV-INs and the red-shifted genetically encoded calcium indicator, jRGECO1a, driven by the Thy1 promoter to allow for simultaneous optogenetic targeting of PV-INs and mesoscopic imaging of excitatory activity. Photothrombosis was induced in the left primary somatosensory forepaw cortex and subsequent optogenetic photostimulation of PV-INs, calcium, and hemodynamic imaging was conducted pre- and post-stroke to map PV-IN circuitry and assess changes in cortical activity.Preliminary results revealed significant disruptions in homotopic resting-state functional connectivity and cortical activity one-week post-stroke. Power maps indicated reduced activity in the somatosensory, hindpaw, and parietal cortices, with electrical forepaw stimulation showing decreased activity in both left and right primary somatosensory forepaw regions. Contralesional excitation increased in the retrosplenial and parietal cortices during forepaw stimulation. Further, optogenetic stimulation of PV-INs pre-stroke showed increased inhibition, while post-stroke stimulation resulted in less ipsilesional inhibition and more global excitation. Behavioral assessments using the cylinder rearing test indicated a 26% decrease in right forepaw use post-stroke, aligning with imaging findings.Ongoing studies aim to extend these observations by including a larger cohort of aged mice and a cohort of young mice at 1-, 4-, and 8- weeks post-stroke to examine age-related differences in PV-IN-mediated plasticity during stroke recovery. These studies will elucidate the critical contributions of PV-INs to post-stroke plasticity and recovery, potentially guiding new therapeutic approaches for stroke rehabilitation.
Abstract WP202: Computed Tomography Perfusion-Based Imaging Score Outperform Other Imaging Scores in Basilar Artery Occlusions – An Agreement Study
Stroke, Volume 56, Issue Suppl_1, Page AWP202-AWP202, February 1, 2025. Background:Several semi-quantitative imaging scores exist to assess the extent of ischemic injury in basilar artery occlusions using various computed tomography (CT)-based modalities. Their inter-rater agreement has never been compared.Methods:We conducted a retrospective multicenter cohort study of patients with basilar artery occlusions. Four imaging scores (PC-ASPECTS, CAPS, BATMAN, and PC-CTA) were assessed by two raters. Inter-rater agreement was compared using Cohen’s kappa statistic and reliability was assessed using the intraclass correlation coefficient (ICC).Results:98 patients were included for analysis. The CT perfusion-based CAPS score yielded the highest interrater agreement (kappa 0.64 [95%CI 0.52 – 0.75]) and highest reliability (ICC 0.82 [95%CI 0.73 – 0.91]). By comparison, CTA-based scores achieved fair agreement. The PC-ASPECTS score yielded the lowest levels of agreement overall (kappa 0.11 [95%CI 0.0061 – 0.21]) and in individual regions, with the lowest kappa values for midbrain (kappa 0.098 [95%CI 0.022 – 0.30]). Dichotomization resulted in some improvement in agreement for all approaches.Conclusion:CT Perfusion-based imaging score provide the highest interrater agreement and reliability for assessment of ischemic injury in patients with basilar artery occlusions among common posterior circulation scoring methodologies.
Abstract WP227: Physiological Magnetic Resonance Imaging Biomarkers for Early Detection of Microvascular Dysfunction in Acute Intracerebral Hemorrhage
Stroke, Volume 56, Issue Suppl_1, Page AWP227-AWP227, February 1, 2025. Introduction:Intracerebral hemorrhage (ICH) is commonly associated with poor neurologic outcomes. Early intervention has been shown to improve patient prognosis, highlighting the necessity of sensitive biomarkers. In this study, we aim to explore the potential of magnetic resonance imaging (MRI)-based physiological parameters for detecting microvascular dysfunction in an acute ICH mouse model.Methods:Young (5 months old, N=2) and aged (22 months old, N=2) C57BL/6 male mice were utilized. ICH was induced via a stereotaxic intra-striatal injection of collagenase. These mice were scanned before and 1 day after surgery longitudinally. We employed a range of non-invasive MRI techniques at 11.7T to characterize microvascular dysfunctions. These techniques included: (a) spin echo MRI for brain volume, (b) T2-relaxation-under-spin-tagging (TRUST) and phase contrast MRI for cerebral metabolic rate of oxygen (CMRO2), (c) arterial spin labeling MRI for regional cerebral perfusion, and (d) water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST) MRI for blood-brain-barrier (BBB) permeability.Results:Brain volume demonstrated a significant age effect (linear mixed effect [LME] model: P=0.044), but was not significantly influenced by ICH, indicating negligible brain dwelling at the examined timepoints. TRUST imaging reveals distinct patterns of change from baseline to ICH between young and aged mice (Fig. 1A). A significant ICH-by-age interaction effect (LME: P=0.004) suggests that the impact of ICH on brain metabolism varies between young and aged mice. ICH-affected brain regions were identifiable in the perfusion maps for both age groups with hemorrhagic areas showing associated hypoperfusion, as indicated by the arrows (Fig. 2). In terms of BBB function, there was a notable reduction in the WEPCAST signal observed around the great vein of Galen (arrows in Fig. 3A). The significant ICH-by-age effect on the permeability-by-area-product (PS) (P=0.006, Fig. 3B) of LME analysis indicates that aged mice are more vulnerable to the BBB disruption following ICH.Conclusion:Our study highlights the potential of physiological imaging biomarkers for detecting early microvascular dysfunctions in ICH. Specifically, functional parameters (i.e., CMRO2and BBB permeability) show promise as sensitive indicators for the early detection of ICH. These biomarkers could facilitate timely interventions, potentially improving outcomes for stroke patients.
Abstract WP262: Prediction of Final Ischemic Infarct Volume Via Virtual Noncontrast Imaging After Stroke Thrombectomy
Stroke, Volume 56, Issue Suppl_1, Page AWP262-AWP262, February 1, 2025. Introduction:Early prediction of final infarct volume is a vital component of clinical recovery. Ischemic infarct volume is an independent predictor of stroke prognosis with larger volumes nonlinearly correlating to worse outcomes. Virtual non contrast imaging (VNC) is a dual-energy computed tomography head (CTH) utilized in differentiating post-thrombectomy contrast staining from hemorrhage due to reperfusion injury. Studies show VNC improves visualization of early infarcts and can be a reliable predictor of final infarct volume. This study investigates difference between initial VNC infarct and final CTH infarct volumes as well as association with modified Rankin Scale (mRS).Methods:This is a retrospective, observational, single-center study of 14 patients who underwent mechanical thrombectomy for acute ischemic stroke between January 2023 and August 2024. Inclusion and exclusion criteria and exclusion flowchart are listed in Figure 1 and 2, respectively. Demographics, National Institute of Health Stroke Scale (NIHSS) and mRS data were extracted from the electronic medical record. Infarct volumes on initial VNC and final CTH were measured using the ABC/2 or ABC/3 formula for ellipsoid or irregular infarcts, respectively. Statistical analysis was conducted with a paired t-test (p-value
Case 4-2025: A 41-Year-Old Man with Syncope, Ankle Swelling, and Abnormal Chest Imaging
New England Journal of Medicine, Volume 392, Issue 5, Page 495-503, January 30, 2025.
Non-contrast magnetic resonance imaging versus ultrasonography for hepatocellular carcinoma surveillance: A randomized, single-center trial
This study aimed to compare ultrasonography (US) and non-contrast magnetic resonance imaging (MRI) in the surveillance of hepatic malignancy.
Usefulness of Myelin Quantification Using Synthetic Magnetic Resonance Imaging for Predicting Outcomes in Patients With Acute Ischemic Stroke
Stroke, Ahead of Print. BACKGROUND:Synthetic magnetic resonance imaging (MRI) is an innovative MRI technology that enables the acquisition of multiple quantitative values, including T1 and T2 values, proton density, and myelin volume, in a single scan. Although the usefulness of myelin measurement with synthetic MRI has been reported for assessing several diseases, investigations in patients with stroke have not been reported. We aimed to explore the utility of myelin quantification using synthetic MRI in predicting outcomes in patients with acute ischemic stroke.METHODS:Patients with acute ischemic stroke (n=101) with a premorbid modified Rankin Scale score ≤2 were enrolled. We performed MRI with a 3 T scanner, acquiring synthetic MRI data in addition to data acquired using the routine protocol; we measured total myelin volume (TMV) using synthetic MRI software. After hospitalization, a synthetic MRI was performed when the patient’s condition was stable, with a median of 7 days from onset to MRI. We examined the factors related to good stroke outcomes (defined by a modified Rankin Scale score of ≤2 at 3 months).RESULTS:Patients with larger TMV were younger, were more frequently male, and had higher body mass index. In addition, TMV was associated with the severity of white matter hyperintensities and total small vessel burden scores. The patients with good outcomes (n=66) had larger TMVs than those without (144.85±22.19 versus 126.62±21.81 mL,P
Cost-utility analysis of MR imaging-guided transurethral ultrasound ablation for the treatment of low- to intermediate-risk localised prostate cancer
Background
Magnetic resonance-guided transurethral ultrasound ablation (MR-TULSA) is a new focal therapy for treating localised prostate cancer that is associated with fewer adverse effects (AEs) compared with established treatments. To support large-scale clinical implementation, information about cost-effectiveness is required.
Objective
To evaluate the cost–utility of MR-TULSA compared with robot-assisted radical prostatectomy (RARP), external beam radiation therapy (EBRT) and active surveillance (AS) for patients with low- to favourable intermediate-risk localised prostate cancer.
Design, setting and participants
A Markov model was developed targeting 60-year-old men diagnosed with low- to intermediate-risk localised prostate cancer over a time horizon of 40 years from the German Statutory Health Insurance (SHI) perspective. To assess the robustness of the results, deterministic and probabilistic sensitivity analyses were performed.
Intervention
Four different treatment strategies were compared: minimally invasive MR-TULSA, two definitive approaches (RARP and EBRT) and one observational strategy (AS).
Outcome measurements and statistical analysis
Outcomes were measured in overall costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER).
Results
AS generated the highest number of QALYs (12.67), followed by MR-TULSA (12.35), EBRT (12.35) and RARP (12.20). RARP generated the lowest costs ( 46 997) over one patient’s lifetime, while MR-TULSA was a slightly more expensive alternative (48 826). The incremental cost-effectiveness ratio (ICER) of AS compared with RARP was 11 600 per QALY and of MR-TULSA compared with RARP was 12 193 per QALY, while EBRT was dominated. At a willingness-to-pay of 20 000 per QALY, the probability of being cost-effective is 44% for AS, 25% for RARP, 25% for MR-TULSA and 6% for EBRT.
Conclusions
All treatment options for 60-year-old men diagnosed with low- to intermediate-risk localised prostate cancer are affected by considerable uncertainty. Accepting high follow-up costs by applying a higher willingness-to-pay, AS is the most favourable treatment option.
Impact of Subarachnoid Hemorrhage on Human Glymphatic Function: A Time-Evolution Magnetic Resonance Imaging Study
Stroke, Ahead of Print. BACKGROUND:Subarachnoid hemorrhage (SAH) is associated with significant mortality and morbidity. The impact of SAH on human glymphatic function remains unknown.METHODS:This prospective, controlled study investigated whether human glymphatic function is altered after SAH, how it differs over time, and possible underlying mechanisms. Glymphatic enrichment was examined by intrathecal contrast-enhanced magnetic resonance imaging (MRI, glymphatic MRI), utilizing the MRI contrast agent gadobutrol (Gadovist, Bayer AG, GE; 0.50 mmol) as a cerebrospinal fluid (CSF) tracer. The distribution of the tracer in the brain and the subarachnoid and ventricular CSF spaces was assessed using standardized multi-phase MRI T1 sequences, and between-group differences in percentage change of standardized T1 signal unit ratios over time were analyzed by linear mixed models.RESULTS:The study comprised 27 patients with SAH (19 female/8 male; 59.3±10.2 years) who were examined 12 months (n=7) after bleed. A sex- and age-matched control group of 22 individuals (15 female/7 male; 55.5±10.5 years) underwent the same glymphatic MRI protocol but had no neurological or CSF disease. The patients with SAH showed a marked impairment of glymphatic enrichment throughout the brain (particularly addressing the cerebral cortex and subcortical white matter), especially after 24 hours. The glymphatic impairment was accompanied by redistribution of CSF tracer from subarachnoid spaces toward ventricles. These alterations were most pronounced after 3 to 6 months and less after 12 months, though with interindividual variation. CSF tracer transport within perivascular subarachnoid spaces was impaired and coincided with impaired glymphatic enrichment.CONCLUSIONS:Human glymphatic function is severely impaired by SAH, particularly shortly after the event. Glymphatic failure is associated with redistribution of CSF from subarachnoid spaces toward ventricles. SAH-related impairment of fluid transport within perivascular subarachnoid spaces may contribute to reduced glymphatic influx. Since patient groups are small, care should be made when concluding about the impact of time on glymphatic function.
Evolution of Imaging Techniques in Ischemic Stroke
Stroke, Ahead of Print.
Epidemiological features of uterine fibroid-associated imaging changes in Chinese women of reproductive age: a retrospective study
Objectives
To investigate uterine fibroid (UF)-associated imaging changes, and their prevalence, incidence and potential risk factors in the Chinese population.
Design
This was a retrospective observational study using health examination data.
Setting
A physical examination centre in Nanchong, China, between October 2017 and December 2020.
Participants
A total of 33 915 Chinese women older than 15 years of age underwent uterine imaging during the study period.
Primary and secondary outcome measures
This study identified entries of UF-associated imaging changes through a two-round expert consultation and calculated prevalence and incidence of UF-associated imaging changes. Logistic regression estimated the association (OR, 95% CI of body mass index, high blood pressure (HBP), blood lipid profile, and fasting blood glucose level) with UF-associated imaging changes. Age-stratified (≤40 years and >40 years) risks were ascertained.
Results
Besides the entry ‘Potential UF’, 17 other entries of UF-associated imaging changes screened by the expert consultation were included, involving a total of 46 864 records (n=33 915), and crude prevalence=25.18%; crude incidence density/1000-woman-years=63.28. Incidence and prevalence increased with age during reproductive age (15–49 years) and decreased thereafter. The greatest burden was in women aged 40–54 years, the prevalence was 38.60%–45.38% and the incidence was 14.73%–17.96%. In the incident younger population (age ≤40 years), overweight (OR: 1.48, 95% CI 1.03 to 2.14) and HBP (OR: 2.16, 95% CI 1.10 to 4.24) were associated with a higher risk for UF-associated imaging changes; in the >40 years group, no association was observed.
Conclusion
UF incidence and prevalence in Asians were higher than previously reported, showed age-related increase in reproductive age, and UF incidence increased with overweight and HBP in ≤40-year-old participants. Variation in UF burden and factors with higher risk noted in different age ranges, and the correlations identified in younger women make it possible for early preventive measures for women with a higher risk of UF.
Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial
Stroke, Ahead of Print. BACKGROUND:Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.METHODS:Patients with ischemic stroke presenting 4.5 to 24 hours from the last known well, with a favorable penumbral profile and an associated large/medium vessel occlusion, were randomized 1:1 to either 0.25 mg/kg tenecteplase or the best medical treatment. A favorable penumbral profile was defined as a hypoperfusion lesion volume to infarct core volume ratio >1.2, with an absolute volume difference >10 mL, and an ischemic core volume 50% of the involved ischemic territory. Secondary outcomes included recanalization, infarct growth, major neurological improvements, change in the National Institutes of Health Stroke Scale score, hemorrhagic transformation within 24 to 48 hours, systemic bleeding at discharge, and modified Rankin Scale (score 0–1, score 0–2, score 5–6, and modified Rankin Scale distribution) at 90 days. The comparison of the primary outcome between groups was conducted using modified Poisson regression with a log-link function and robust error variance, adjusted for time from the last known well to randomization, the site of vessel occlusion, and planned endovascular treatment.RESULTS:Among 224 enrolled patients, 111 were assigned to receive tenecteplase and 113 to receive the best medical treatment (including 23% [n=26] of participants who received intravenous tissue-type plasminogen activator). The mean (SD) age of the tenecteplase group and the best medical treatment group was 64.2 (10.4) and 63.6 (11.0) years old, with 72.1% (n=80) and 70.8% (n=80) male enrolled, respectively. A proportion of 54.9% (n=123) of patients were transferred to the catheter room for preplanned endovascular treatment. The primary outcome occurred in 33.3% (n=37) of the tenecteplase group versus 10.8% (n=12) in the best medical treatment group (adjusted relative risk, 3.0 [95% CI, 1.6–5.7];P=0.001). Tenecteplase significantly increased the recanalization rate compared with the best medical treatment (35.8% [n=39] versus 14.3% [n=16], adjusted relative risk, 2.5 [95% CI, 1.4–4.4];P=0.002). There were no significant differences in clinical efficacy outcomes or rates of hemorrhagic transformation between the groups.CONCLUSIONS:Administered at a dose of 0.25 mg/kg intravenously, tenecteplase increased reperfusion without symptomatic intracranial hemorrhage in patients with ischemic stroke selected by imaging in late-time window treatment but did not change clinical outcomes at 90 days.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT04516993.
Transcranial Cortex-Wide Imaging of Murine Ischemic Perfusion With Large-Field Multifocal Illumination Microscopy
Stroke, Volume 56, Issue 1, Page 170-182, January 1, 2025. BACKGROUND:Ischemic stroke is a common cause of death worldwide and a main cause of morbidity. Presently, laser speckle contrast imaging, x-ray computed tomography, and magnetic resonance imaging are the mainstay for stroke diagnosis and therapeutic monitoring in preclinical studies. These modalities are often limited in terms of their ability to map brain perfusion with sufficient spatial and temporal resolution, thus calling for development of new brain perfusion techniques featuring rapid imaging speed, cost-effectiveness, and ease of use.METHODS:We report on a new preclinical high-resolution angiography technique for murine ischemic stroke imaging based on large-field high-speed multifocal illumination fluorescence microscopy. We subsequently showcase the proposed method by monitoring therapeutic effects of thrombolysis in stroke (n=6), further performing cross-strain comparison of perfusion dynamics (n=6) and monitoring the therapeutic effects of sensory stimulation–based treatment (n=11).RESULTS:Quantitative readings of hemodynamic and structural changes in cerebral vascular network and pial vessels were attained with 14.4-µm spatial resolution at 80-Hz frame rate fully transcranially. The in vivo perfusion maps accurately delineated the ischemic core and penumbra, further exhibiting a strong correlation (86.1±4.5%) with ex vivo triphenyl tetrazolium chloride staining, significantly higher than for the conventional laser speckle contrast imaging method. Monitoring of therapeutic effects of thrombolysis confirmed that early recanalization could effectively save the penumbra while reducing the infarct area. Cross-strain comparison of perfusion dynamics affirmed that C57BL/6 mice feature a larger penumbra and smaller infarct core as compared with BALB/c mice, which have few or no collaterals. Sensory stimulation–based treatment could effectively enhance blood flow and abolish perfusion deficits in the ischemic core and penumbra regions.CONCLUSIONS:A high-speed fluorescence-based angiography method for transcranial stroke imaging in mice is introduced, which is capable of localizing brain perfusion changes and accurately assessing the ischemic penumbra. Compared with the whole-brain x-ray computed tomography and magnetic resonance imaging methods, which are conventionally used for stroke diagnosis and therapeutic monitoring, the new approach is simple and cost-effective, further offering high resolution and speed for in vivo studies. It thus opens new venues for brain perfusion research under various disease conditions such as stroke, neurodegeneration, or epileptic seizures.
Penumbral Imaging to Guide Endovascular Treatment for M2 Middle Cerebral Artery Stroke
Stroke, Ahead of Print. BACKGROUND:A potential benefit of mechanical thrombectomy for patients with distal medium vessel occlusions is currently being investigated in randomized trials. Computed tomography perfusion imaging has not yet been tested as a method to guide mechanical thrombectomy for distal medium vessel occlusions. The purpose of this study was to assess penumbral imaging as an imaging-based method for triaging patients with ischemic stroke and acute M2-middle cerebral artery occlusion.METHODS:This observational retrospective study of M2-middle cerebral artery patients with ischemic stroke triaged by multimodal computed tomography undergoing mechanical thrombectomy at a high-volume stroke center between January 2015 and January 2023. The effect of recanalization was analyzed according to computed tomography perfusion-derived lesion volumes (defined using relative cerebral blood flow 6 seconds) using logistic regression analysis, and interaction terms between the independent variables and recanalization were tested. The primary end point was functional independence at day 90, defined using modified Rankin Scale scores of 0 to 2.RESULTS:A total of 140 patients with M2-middle cerebral artery occlusion were included. In multivariable logistic regression analysis, recanalization was not associated with better functional outcome (adjusted odds ratio, 1.85 [95% CI, 0.87–3.90];P=0.11). After including interaction terms, a significant treatment effect between recanalization and computed tomography perfusion-derived lesion volumes was observed in patients with >150 mL hypoperfusion volume (adjusted odds ratio, 1.02 [95% CI, 1.00–1.03];P=0.007) or >125 mL penumbral volumes (adjusted odds ratio, 1.02 [95% CI, 1.01–1.03];P=0.005), as well as for baseline ischemic core volume within the range of 15 to 40 mL (adjusted odds ratio, 1.11 [95% CI, 1.01–1.22];P=0.03).CONCLUSIONS:Penumbral imaging might serve as a useful tool for treatment decision-making in distal medium vessel occlusions, particularly in cases of suspected non- or codominant M2-middle cerebral artery vessel occlusions. A hypoperfusion volume threshold of >150 mL emphasizes the potential value of computed tomography perfusion as a standardized tool directly showing the volumetric relevance in distal medium vessel occlusion cases.
In Vivo Cardiovascular Molecular Imaging: Contributions to Precision Medicine and Drug Development
Circulation, Volume 150, Issue 23, Page 1885-1897, December 3, 2024. Conventional forms of noninvasive cardiovascular imaging that evaluate morphology, function, flow, and metabolism play a vital role in individual treatment decisions, often based on guidelines. Innovations in molecular imaging have enhanced our ability to spatially quantify the expression of a wider array of disease-related proteins, genes, or cell types, or the activity of specific pathogenic pathways. These techniques, which usually rely on design of targeted imaging probes, have already been used extensively in cancer medicine and have now become part of cardiovascular care in conditions such as amyloidosis and sarcoidosis. The recognition that common cardiovascular conditions are caused by a substantial diversity of pathobiologic pathways and the diversity of therapies available for use have rekindled interest in expanding the role of molecular imaging of tissue phenotype to improve precision in diagnosis and therapeutic decision-making. The intent of this article is to raise awareness and understanding of approaches to molecular or cellular imaging of phenotype with targeted probes, and their potential to promote the principles of precision medicine. Also addressed are the diverse roles of molecular imaging to improve precision and efficiency of new drug development at the stages of candidate identification, preclinical testing, and clinical trials.