Frank Prato

• PhD, FCCPM, ABMP, FCOMP
• Managing Director at Lawson Health Research Institute

Introduction: T2* cardiac MRI (CMR) is the standard for detecting hemorrhagic myocardial infarction (MI). However, the conventional T2* CMR (2D breath-held, ECG-gated, multi-gradient-echo T2*) can suffer from limited spatial resolution and multiple motion artifacts. We developed a time-efficient, fully ungated, free breathing, 3D T2* mapping method...

To detect cellular activities deep within the body using magnetic resonance platforms, magnetosomes are the ideal model of genetically-encoded nanoparticles. These membrane-bound iron biominerals produced by magnetotactic bacteria are highly regulated by approximately 30 genes; however, the number of magnetosome genes that are essential and/or cons...

The magnetosome, a membrane-bound iron biomineral formed within magnetotactic bacteria, is a unique model for a magnetic resonance imaging (MRI) reporter gene contrast agent. We are translating this technology to mammalian cells by expressing essential magnetosome genes mamI, mamL, mamB, and mamE into MDA-MB-435 human melanoma cells. Currently, the...

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post-myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the...

Bacteria constitute a significant part of the biomass of the human microbiota, but their interactions are complex and difficult to replicate outside the host. Exploiting the superior resolution of magnetic resonance imaging (MRI) to examine signal parameters of selected human isolates may allow tracking of their dispersion throughout the body. Here...

INTRODUCTION Cerebral small vessel disease (SVD) and amyloid beta (Aβ) pathology frequently co‐exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood. METHODS In a unique cohort of mixed Alzheimer's disease and moderate–severe...

Magnetosomes are organelle-like structures within magnetotactic bacteria that store iron biominerals in membrane-bound vesicles. In the bacteria, formation of these structures is highly regulated by approximately 30 genes which are conserved throughout different species. To compartmentalize iron in mammalian cells for magnetic resonance imaging usi...

To detect cellular activities deep within the body using magnetic resonance platforms, magnetosomes are the ideal model of genetically-encoded nanoparticles. These membrane-bound iron biominerals produced by magnetotactic bacteria are highly regulated by approximately 30 genes; however, only a few magnetosome genes are essential and may constitute...

Bacteria constitute a significant part of the biomass of the human microbiota, but their interactions are complex and difficult to replicate outside the host. Exploiting the superior resolution of magnetic resonance imaging (MRI) to examine signal parameters of selected human isolates may allow tracking of their dispersion throughout the body. We i...

Background After myocardial infarction, fibrosis and an ongoing dysregulated inflammatory response have been shown to lead to adverse cardiac remodeling. FDG PET is an imaging modality sensitive to inflammation as long as suppression protocols are observed while gadolinium enhanced MRI can be used to determine extracellular volume (ECV), a measure...

Myocardial infarction (MI) remains a leading cause of morbidity and mortality. In atherothrombotic MI (ST-elevation MI and type 1 non-ST-elevation MI), coronary artery occlusion leads to ischemia. Subsequent cardiomyocyte necrosis evolves over time as a wavefront within the territory at risk. The spectrum of ischemia and reperfusion injury is wide:...

Background Left-sided breast cancer patients receiving adjuvant radiotherapy are at risk for coronary artery disease, and/or radiation mediated effects on the microvasculature. Previously our laboratory demonstrated in canines with hybrid ¹⁸FDG/PET a progressive global inflammatory response during the initial one year following treatment. In this s...

Our purpose was to investigate the utility of 18F-FDG PET/MRI and serial blood work to detect early inflammatory responses and cardiac functionality changes at 1 mo after radiation therapy (RT) in patients with left-sided breast cancer. Methods: Fifteen left-sided breast cancer patients who enrolled in the RICT-BREAST study underwent cardiac PET/MR...

Many chronic inflammatory conditions are mediated by an increase in the number of monocytes in peripheral circulation, differentiation of monocytes to macrophages, and different macrophage subpopulations during pro- and anti-inflammatory stages of tissue injury. When hepcidin secretion is stimulated during inflammation, the iron export protein ferr...

White matter (WM) injury is frequently observed along with dementia. Positron emission tomography with amyloid-ligands (Aβ-PET) recently gained interest for detecting WM injury. Yet, little is understood about the origin of the altered Aβ-PET signal in WM regions. Here, we investigated the relative contributions of diffusion MRI-based microstructur...

Purpose/Objective(s) The goal of this study is to investigate the utility of hybrid ¹⁸FDG PET/MRI and serial blood work to detect early inflammatory response and cardiac functionality changes at one-month and one-year post radiation therapy (RT) in patients with left-sided breast cancer. Materials/Methods Fifteen left-sided breast cancer patients...

It remains unclear to what extent cerebrovascular burden relates to amyloid beta (Aβ) deposition, neurodegeneration, and cognitive dysfunction in mixed disease populations with small vessel disease and Alzheimer's disease (AD) pathology. In 120 subjects, we investigated the association of vascular burden (white matter hyperintensity [WMH] volumes)...

Background Atrial fibrillation (AF) is associated with extracellular matrix (ECM) remodelling and often coexists with myocardial fibrosis (MF); however, the causality of these conditions is not well established. Objective We aim to corroborate AF to MF causality by quantifying left atrial (LA) fibrosis in cardiac magnetic resonance (CMR) images af...

Bacteria constitute a significant part of the biomass of the human microbiota, but their interactions are complex and difficult to replicate outside the host. Exploiting the superior resolution of magnetic resonance imaging (MRI) to examine signal parameters of selected human isolates may allow tracking of their dispersion throughout the body. We i...

Introduction: Radiotherapy (RT) for non-small cell lung cancer (NSCLC) can cause unintentional cardiac toxicity in many patients. Multi-modality functional cardiac imaging could be used to assess the effects on myocardial perfusion, left ventricular function and the inflammatory response to RT which may be useful in developing future patient-specif...

Background Clinical diagnosis of frontotemporal dementia (FTD) remains a challenge due to the overlap of symptoms among FTD subtypes and with other psychiatric disorders. Perfusion imaging by arterial spin labeling (ASL) is a promising non-invasive alternative to established PET techniques; however, its sensitivity to imaging parameters can hinder...

Background Reperfusion therapy for acute myocardial infarction (MI) is lifesaving. However, the benefit of reperfusion therapy can be paradoxically diminished by reperfusion injury, which can increase MI size. Objectives Hemorrhage is known to occur in reperfused MIs, but whether hemorrhage plays a role in reperfusion-mediated MI expansion is not...

INTRODUCTION: It remains unclear to which extent vascular burden promotes neurodegeneration and cognitive dysfunction in a cohort spanning low-to-severe small vessel disease (SVD) and amyloid-beta pathology. METHODS: In 120 subjects, we investigated 1) whether vascular burden, quantified as total or lobar white matter hyperintensity (WMH) volumes,...

White matter (WM) injury is frequently observed along with dementia. Positron emission tomography with amyloid-ligands (Aβ-PET) recently gained interest for detecting WM injury. Yet, little is understood about the origin of the altered Aβ-PET signal in WM regions. Here, we investigated the relative contributions of diffusion MRI-based microstructur...

Background: Intramyocardial hemorrhage (IMH) within myocardial infarction (MI) is associated with major adverse cardiovascular events. Bright-blood T2*-based cardiovascular magnetic resonance (CMR) has emerged as the reference standard for non-invasive IMH detection. Despite this, the dark-blood T2*-based CMR is becoming interchangeably used with...

Background Advances in the understanding of the pathophysiology of frontotemporal dementia (FTD) and related disorders, along with the development of novel candidate disease modifying treatments, have stimulated the need for tools to assess the efficacy of new therapies. While perfusion imaging by arterial spin labeling (ASL) is an attractive appro...

Background Accurate quantification of radioactivity, measured by an integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) system, is still a challenge. One aspect of such a challenge is to correct for the hardware attenuation, such as the patient table and radio frequency (RF) resonators. For PET/MRI systems, computed t...

Objective: Hybrid PET/MRI may improve detection of seizure-onset zone (SOZ) in drug-resistant epilepsy (DRE), however, concerns over PET bias from MRI-based attenuation correction (MRAC) have limited clinical adoption of PET/MRI. This study evaluated the diagnostic equivalency and potential clinical value of PET/MRI against PET/CT in DRE. Materials...

Background and Purpose To quantify intra-fraction tumor motion using imageguidance and implanted fiducial markers to determine if a 5mm planning-target-volume (PTV) margin is sufficient for early stage breast cancer patients receiving neoadjuvant stereotactic ablative radiotherapy (SABR). Materials and Methods A HydroMark© (Mammotome) fiducial was...

Background The aims of this study were to investigate the application of a constant infusion (CI) to mitigate the issue of constantly changing Gd-DTPA contrast levels in a bolus injection for extracellular volume (ECV) measurements by (a) comparing a CI alone to a bolus alone and a bolus followed by CI in healthy myocardium, (b) evaluating the impa...

Background Following myocardial infarction, tissue undergoes pathophysiological changes involving inflammation and scar tissue formation. However, little is known about the pathophysiology and prognostic significance of any corresponding changes in remote myocardium. The aim of this study was to investigate the potential application of a combined c...

We quantitatively investigate the influence of image registration, using open-source software (3DSlicer), on kinetic analysis (Tofts model) of dynamic contrast enhanced MRI of early-stage breast cancer patients. We also show that registration computation time can be reduced by reducing the percent sampling (PS) of voxels used for estimation of the...

Background: Hybrid PET/MRI can non-invasively improve localization and delineation of the epileptic focus (EF) prior to surgical resection in medically refractory epilepsy (MRE), especially when MRI is negative or equivocal. In this study, we developed a PET-guided diffusion tractography (PET/DTI) approach combining 18F-fluorodeoxyglucose PET (FDG-...

Purpose: The aim of this study was to evaluate random forests (RFs) to identify ROIs on F-florbetapir and F-FDG PET associated with Montreal Cognitive Assessment (MoCA) score. Materials and methods: Fifty-seven subjects with significant white matter disease presenting with either transient ischemic attack/lacunar stroke or mild cognitive impairm...

Background: Simultaneous cardiovascular imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI) requires tools such as radio frequency (RF) phased arrays to achieve high temporal and spatial resolution in the MRI, as well as accurate quantification of PET. Today, high-density phased arrays (> 16 channels) used for card...

Background Despite advances, blood oxygen level-dependent (BOLD) cardiac MRI for myocardial perfusion is limited by inadequate spatial coverage, imaging speed, multiple breath holds, and imaging artifacts, particularly at 3.0 T. Purpose To develop and validate a robust, contrast agent-unenhanced, free-breathing three-dimensional (3D) cardiac MRI ap...

Magnetic resonance imaging can be used to track cellular activities in the body using iron-based contrast agents. However, multiple intrinsic cellular iron handling mechanisms may also influence the detection of magnetic resonance (MR) contrast: a need to differentiate among those mechanisms exists. In hepcidin-mediated inflammation, for example, d...

Hybrid PET/MR imaging is an emerging imaging modality combining positron emission tomography (PET) and magnetic resonance imaging (MRI) in the same system. Since the introduction of clinical PET/MRI in 2011, it has had some impact (e.g., imaging the components of inflammation in myocardial infarction), but its role could be much greater. Many oppor...

Purpose: To determine the effect of dose fractionation and time delay post-neoadjuvant stereotactic ablative radiotherapy (SABR) on dynamic contrast-enhanced (DCE)-MRI parameters in early stage breast cancer patients. Materials and methods: DCE-MRI was acquired in 17 patients pre- and post-SABR. Five patients were imaged 6-7 days post-21 Gy/1fra...

Background Cardiovascular imaging using hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI) requires a radio frequency phased array resonator capable of high acceleration factors in order to achieve the shortest breath-holds while maintaining optimal MRI signal-to-noise ratio (SNR) and minimum PET photon attenuation. To o...

Background: Characterization of left atrial (LA) hemodynamics in paroxysmal atrial fibrillation (PAF) may provide valuable insights for thromboembolic risk. Purpose: To evaluate LA vortex formation and velocity distributions by 4D flow MRI and identify associations with age, LA/LV (left ventricle) function, and established risk scores. Study ty...

Purpose: To evaluate random forests (RFs) as a supervised machine learning algorithm to classify amyloid brain PET as positive or negative for amyloid deposition and identify key regions of interest for stratification. Methods: The data set included 57 baseline F-florbetapir (Amyvid; Lilly, Indianapolis, IN) brain PET scans in participants with...

Magnetic resonance imaging (MRI) is a non-invasive imaging modality used in longitudinal cell tracking. Previous studies suggest that MagA, a putative iron transport protein from magnetotactic bacteria, is a useful gene-based magnetic resonance contrast agent. Hemagglutinin-tagged MagA was stably expressed in undifferentiated embryonic mouse terato...

Myocardial oxygenation—the ability of blood vessels to supply the heart muscle (myocardium) with oxygen—is a critical determinant of cardiac function. Impairment of myocardial oxygenation is a defining feature of ischemic heart disease (IHD), which is caused by pathological conditions that affect the blood vessels supplying oxygen to the heart musc...

This poster summarizes my work on the investigation of extracting an image-derived input function from the carotid arteries of small animals. We hope that this work sets the groundwork for further investigation into this source of an image-derived input function. This will allow users of PET imaging systems whose axial field-of-view is not large e...

Significant advances in positron emission tomography (PET) and magnetic resonance imaging (MRI) brain imaging in the early detection of dementia indicate that hybrid PET/MRI would be an effective tool to screen for dementia in the population living with lifestyle risk factors. Here we investigate the associated costs and benefits along with the nee...

Background and purpose: This study aimed to determine the effects of reducing the dose of contrast agent (CA) in a DCE-MRI scan on inter- and intra-observer variability in the context of MRI-guided target volume delineation for stereotactic body radiation therapy of early stage breast cancer patients. This is in hopes of reducing risks to patients...

Background Inflammatory cardiac disorders, in particular, sarcoidosis, play an important role in left ventricular dysfunction, conduction abnormalities, and arrhythmias. In this study, we compared the imaging characteristics and diagnostic information obtained when patients were imaged sequentially with PET/CT and then with hybrid PET/MRI on the sa...

We have previously proposed that there are at least two initial molecular transduction mechanisms needed to explain specific and nonspecific biological effects of weak magnetic fields. For the specific effect associated with animal magnetic navigation, the radical pair mechanism is the leading hypothesis; it associates the specialised magnetic sens...

Background: [18F]-fluorodeoxyglucose (18FDG) uptake imaged with positron emission tomography (PET) and computed tomography (CT) may serve as a biomarker of plaque inflammation. This study evaluated the relationship between carotid plaque 18FDG uptake and a) intraplaque expression of macrophage and macrophage-like cellular CD68 immunohistology; b)...

While positron emission tomography (PET) with15O-water is the gold standard for imaging cerebral blood flow (CBF), quantification requires measuring the arterial input function (AIF), which is an invasive and noisy procedure. To circumvent this problem, we propose a non-invasive PET/ magnetic resonance (MR) approach that eliminates the need to meas...

The radical pair mechanism is a leading hypothesis in animal magnetic navigation. This mechanism associates the magnetic sense with the visual system, the radical pairs in cryptochromes of the eye retina being specialized magnetic receptors that modulate rhodopsin-mediated photoreception. There are also nonspecific magnetic effects in biology, whic...

To identify molecular activities that define the early stages of disease progression, there is a critical need to noninvasively image these processes. For this, the magnetosome is an ideal structure by which cellular and molecular magnetic resonance imaging (MRI) may be refined. Within the design of this magnetotactic bacterial compartment lies the...

Purpose: The clinical utility of FDG-PET in diagnosing frontotemporal dementia (FTD) has been well demonstrated over the past decades. On the contrary, the diagnostic value of arterial spin labelling (ASL) MRI – a relatively new technique – in clinical diagnosis of FTD has yet to be confirmed. Using simultaneous PET/MRI, we evaluated the diagnosti...

During interplanetary flights in the near future, a human organism will be exposed to prolonged periods of a hypomagnetic field that is 10,000 times weaker than that of Earth’s. Attenuation of the geomagnetic field occurs in buildings with steel walls and in buildings with steel reinforcement. It cannot be ruled out also that a zero magnetic field...

Purpose: The purpose of this study was to describe and evaluate methods for calculating a megavoltage computed tomography (MVCT) derived MR hardware attenuation map (μ-map) and dual-energy CT (DECT) for 511 keV photons. Methods: Phantom measurements were acquired on a whole-body hybrid PET/MRI system, using a four-channel receive-only MR radiofr...

Myocardial blood flow (MBF) is the critical determinant of cardiac function. However, its response to increases in partial pressure of arterial CO2 (PaCO2), particularly with respect to adenosine, is not well characterized due to challenges in blood gas control and limited availability of validated approaches to ascertain MBF in vivo. By prospectiv...

Background: Emerging evidence indicates that persistent microvascular obstruction (PMO) is more predictive of major adverse cardiovascular events than myocardial infarct (MI) size. But it remains unclear how PMO, a phenomenon limited to the acute/subacute period of MI, drives adverse remodeling in chronic MI setting. We hypothesized that PMO resol...

Proposed is a general physical mechanism of magnetoreception of weak magnetic fields (MFs). The mechanism is based on classical precessional dynamics of a magnetic moment in a thermally disturbed environment and includes a minimum of necessary parameters—the gyromagnetic ratio, thermal relaxation time, and rate of downstream events generated by cha...

Target Audience: This study may be of interest for clinicians and clinical researchers who study or measure left atrial blood flow. Purpose: Atrial fibrillation (AF) is a common cardiac arrhythmia associated with elevated morbidity and mortality 1. The latter are largely contributed to by an elevated risk of systemic thrombo-embolism and stroke lea...

The radionuclidic purity of cyclotron-produced 99mTc has been measured by gamma ray spectroscopy and compared to the results of a quick release test modeled after the molybdenum breakthrough test performed on generator-derived 99mTc. Excellent radionuclidic purity is reported for samples produced at BCCA during our clinical trial. The quick release...

Purpose:Dynamic contrast enhanced (DCE) MRI is applied extensively for diagnosis and treatment monitoring of breast cancer. However, patient motion can introduce artificial variation in the signal enhancement curves. Non-rigid registration can improve the curves but computation time can be long. Reducing the percentage of the image sampled (PS) can...

Purpose:To monitor the evolution of radiation-induced cardiac inflammation in a canine model using hybrid positron emission tomography (PET/magnetic resonance imaging (MRI). Methods:Research ethics approval was obtained for a longitudinal imaging study of 5 canines after cardiac irradiation. Animals were imaged at baseline, 3 months, 6 months, and...

From the efforts of a number of Canadian institutions and private industry collaborations, direct production of 99mTc using medical cyclotrons has recently been advanced from a 1970's academic exercise to a commercial, economically viable solution for regional production. Using GE PETtrace 880 machines our team has established preliminary saturated...

This is a focused review of imaging literature to scope the utility of hybrid brain imaging in neuropsychiatric disorders. The review focuses on brain imaging modalities that utilize hybrid (fusion) techniques to characterize abnormal brain molecular signals in combination with structural and functional changes that have been observed in neuropsych...

Reporter gene-based labeling of cells with iron is an emerging method of providing magnetic resonance imaging contrast for long-term cell tracking and monitoring cellular activities. This report investigates 9.4 T nuclear magnetic resonance properties of mammalian cells overexpressing MagA, a putative iron transport protein from magnetotactic bacte...

Introduction: Myocardial BOLD MRI is an emerging non-contrast approach for the assessment of ischemic heart disease. Current BOLD MR methods are limited in part by poor spatial coverage, heart rate dependency and image artifacts, particularly at 3T. To address these limitations, we developed a heart-rate independent, free-breathing 3D T2 mapping te...

Using a gene-based approach to track cellular and molecular activity with magnetic resonance imaging (MRI) has many advantages. The strong correlation between transverse relaxation rates and total cellular iron content provides a basis for developing sensitive and quantitative detection of MRI reporter gene expression. In addition to biophysical co...

To identify the presence of low-dose radiation induced cardiac toxicity in a canine model using hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI). Research ethics board approval was obtained for a longitudinal imaging study of 5 canines after cardiac irradiation. Animals were imaged at baseline, 1 week post cardiac irra...