MRI Monitor: In Sequence
By Uzay Emir, PhD, and Stephen Sawiak, PhD
Radiology Today
Vol. 26 No. 7 P. 28
Novel MRI Sequence Enhances Preclinical Imaging
As global health care systems face mounting challenges from pervasive labor shortages and escalating costs, the 2024 Deloitte Global Healthcare Sector Outlook1 highlights the increasing demand for technological advancements that enhance and expedite analytical capabilities. In this context, MRI is transforming its role beyond traditional diagnostics, establishing itself as a powerful tool for investigating molecular and cellular mechanisms in living organisms.
Against this backdrop, a 2025 projection by Nature Medicine2 estimates that the number of individuals living with dementia in the United States— currently the seventh leading cause of death and a major contributor to global disability, according to the World Health Organization3—will nearly double over the next 35 years, resulting in nearly 10 million new cases annually. This growing burden underscores the urgent need for advanced imaging technologies that can detect early microstructural and biochemical brain changes before clinical symptoms emerge.
Recent advances in MRI, especially at high and ultrahigh field strengths, have greatly expanded the ability to noninvasively study neurotransmitter dynamics, microstructure, and energy metabolism in the brain. These developments are accelerating discoveries across various pathologies—including epilepsy, neurodegenerative diseases, brain tumors, and conditions involving autonomic and neuroendocrine dysfunction—by allowing functional, structural, and metabolic imaging within a single modality.
While MRI has traditionally played specific roles in clinical diagnostics and research, its integration into preclinical imaging pipelines has gained momentum as a valuable link between molecular mechanisms and translational results. Preclinical MRI provides a platform for high-resolution validation of new techniques, enabling the improvement of contrast methods, acquisition strategies, and reconstruction algorithms before they are applied in humans. In this context, methods such as PETALUTE not only promote preclinical science but also help reduce risks and accelerate clinical translation by enabling quantitative, artifact-resistant imaging at the molecular and cellular levels (Figure 1).
This article highlights a collaborative effort between Purdue University, the University of North Carolina at Chapel Hill’s Biomedical Research Imaging Center, and the University of Cambridge aimed at advancing the capabilities of preclinical MRI through the development and validation of novel acquisition strategies—most notably the PETALUTE sequence—for high-resolution, multicontrast imaging of both 1H and X-nuclei (eg, 23Na, 31P) signal components. These efforts are designed to enhance sensitivity, minimize artifacts, and facilitate detailed visualization of short-transverse relaxation time (T2*) species and metabolic processes crucial to translational neuroscience and disease modeling.
Improving Image Capture
The researchers aimed to overcome longstanding limitations in ultrashort echo time (UTE) MRI for molecular imaging. Their goal was to improve signal-to-noise ratio (SNR), spatial resolution, and acquisition speed for both 1H-based metabolic imaging and X-nuclei modalities, including 23Na, 31P, 2H, and 13C.
Traditional molecular MRI and MR spectroscopic imaging techniques often involve compromises between spatial resolution, scan time, and sensitivity, especially when targeting low-abundance metabolites, rapidly decaying signals, or nonproton nuclei. Single-voxel or localized spectroscopic methods typically require lengthy acquisition times and have limited spatial coverage. In contrast, conventional techniques may insufficiently sample central or peripheral regions of k-space, thereby reducing quantification accuracy and anatomical detail.
The PETALUTE sequence, a novel 3D dual-echo UTE MRI sequence, tackles these issues with a multiecho UTE design based on a modified rosette k-space trajectory that strategically oversamples both the center and edges of k-space. This approach allows for efficient volumetric imaging of short-T2* species across various nuclei, offering improved SNR and spatial accuracy. Additionally, PETALUTE incorporates a golden angle rotation scheme, which introduces temporal incoherence between repetitions—enabling compressed sensing reconstruction, retrospective temporal binning, and self-gated, motion-resolved imaging (such as respiratory or cardiac gating) without requiring external hardware.
By combining multinuclear compatibility, UTE, and robust self-gating features, PETALUTE creates a versatile and high-quality platform for examining tissue microstructure, ionic environments, and dynamic metabolic activities, pushing the boundaries of preclinical and translational MRI.
In contrast to traditional radial and Cartesian or rosette schemes, PETALUTE increases sampling density in two strategically important regions of k-space: the center, which enhances the SNR and supports self-gated, motion-resolved imaging, and the outer periphery, which improves spatial resolution. Each petal readout starts and ends at the k-space center, allowing two or more echoes per repetition time. This inherent multiecho setup allows for flexible, interleaved contrast generation, quantitative T2* mapping, and compressed sensing-accelerated reconstruction (Figure 2).
Implemented on Bruker’s preclinical MRI platform, PETALUTE showed significant improvements in imaging efficiency and accuracy (Figure 3). The sequence enables high-resolution volumetric imaging with much shorter scan times, while maintaining sensitivity to rapidly decaying signals. By capturing subvoxel contrast details across large tissue volumes, PETALUTE supports comprehensive evaluation of microstructural and metabolic changes with strong translational relevance for neurological, musculoskeletal, and oncological studies.
Accurate Brain Imaging
A 2023 study published in Magnetic Resonance in Medicine4 demonstrated the effectiveness of the PETALUTE sequence in capturing signal components with ultrashort transverse relaxation times in brain tissue—signals that are usually inaccessible to conventional 1H MRI methods. Standard gradient- echo and spin-echo sequences are inherently biased toward long T2 components, resulting in poor sensitivity for rapidly decaying structures, such as tightly bound water pools, macromolecules, or myelin.
PETALUTE, by contrast, operates at echo times in the tens of microseconds, enabling direct imaging of short-T2* species. One of its most promising applications is visualizing the myelin bilayer—a lamellar lipid structure that insulates axons and is crucial for neural conduction and plasticity. Because myelin-associated water signals decay rapidly, traditional MRI sequences cannot capture its signal. PETALUTE’s multiecho UTE framework, combined with center-out rosette sampling, allows reliable detection and spatial localization of myelin signal components.
In addition to 1H-based applications, another recent study5 highlighted PETALUTE’s performance in 31P MR spectroscopic imaging (MRSI), where it showed superior spatial coverage and sensitivity compared with conventional methods. This enables high-resolution mapping of phosphorus-containing metabolites such as adenosine triphosphate (ATP) and phosphocreatine (PCr)—key indicators of cellular energy metabolism—further expanding PETALUTE’s potential in neurological, oncological, and metabolic imaging. This unique ability to detect ultrashort T2* signals with high spatiotemporal accuracy positions PETALUTE as a transformative tool for microstructural and metabolic brain imaging, with significant implications for both basic research and preclinical disease models.
Beyond the Brain
While initially developed for neuroimaging, the PETALUTE sequence has demonstrated significant translational potential across multiple organ systems, including musculoskeletal and abdominal imaging, especially in tissues characterized by rapid signal decay, such as cartilage, bone, and liver. By utilizing UTEs ranging from tens to hundreds of microseconds, PETALUTE enables the direct detection of short-T2* components that are typically invisible to conventional sequences.
One key application is osteoarthritis, a degenerative joint disease affecting over 528 million people worldwide, according to the World Health Organization. 6 Early-stage osteoarthritis involves the loss of glycosaminoglycans from cartilage. Sodium (23Na) MRI provides a noninvasive way to measure glycosaminoglycan content, but traditional sodium imaging faces challenges such as long scan times and low spatial resolution. A clinical study in Skeletal Radiology7 showed that PETALUTE enables in vivo sodium imaging at 3 T with accuracy comparable to standard methods, while reducing scan time by 41%, and it enhances SNR and central k-space sampling for better spatial detail in thin cartilage layers.
Furthermore, PETALUTE has proven effective in 31P MRSI, where rapid signal decay and low resolution have historically limited the ability to quantify metabolic intermediates such as ATP, PCr, and inorganic phosphate. A study by Bozymski et al8 demonstrated that PETALUTE achieves superior point spread function, SNR, and acquisition uniformity compared with traditional 31P-MRSI approaches—advancing noninvasive assessments of energy metabolism in the brain and skeletal muscles.
Importantly, PETALUTE’s design incorporates self-gating through frequent central k-space sampling, enabling retrospective motion correction in anatomies affected by physiological motion, particularly the abdomen, where respiration and peristalsis commonly impair image quality. This makes PETALUTE highly suitable for imaging the liver, kidneys, and gastrointestinal structures and also supports its integration into dynamic imaging protocols.
Specifically, PETALUTE facilitates dynamic contrast-enhanced (DCE) MRI, with its high temporal resolution and multiecho setup enabling tracking of contrast kinetics in vascular and perfusion studies. The sequence’s UTE capabilities allow early-phase contrast detection with enhanced sensitivity to T1 changes, making it ideal for quantitative DCE studies in oncology, liver fibrosis, and renal function evaluation.
In summary, the advances behind PETALUTE, combining ultrashort TE acquisition with efficient k-space sampling, enable detailed multiparametric and multinuclear imaging across various tissues for a wide range of biomedical applications. Its versatility in supporting 23Na, 31P, and, potentially, 2H and 13C imaging; resilience in motionprone contexts; and suitability for both structural and DCE protocols establish it as an all-in-one UTE platform for highimpact translational research.
With robust preclinical results and proven clinical feasibility, PETALUTE bridges the gap between basic science and clinical practice, supporting a unified approach to imaging fast-decaying molecular signals, energy metabolism, and perfusion dynamics. Its combination of motion resilience, multinuclear capabilities, and dynamic imaging positions it as a next-generation framework for both early-phase clinical studies and mechanistic research in animal models.
The potential for PETALUTE to drive discoveries in both clinical and preclinical imaging is increasingly evident. As adoption of this methodology expands across the imaging research community, PETALUTE is being integrated into a growing range of applications, including multiecho spectroscopic imaging, balanced steady-state free precession contrast strategies, and iron oxide nanoparticle quantification in oncology models. Its compatibility with a wide array of pulse sequences and contrast mechanisms, combined with its motion resilience and rapid acquisition, makes PETALUTE a versatile platform capable of accelerating biomarker development and translational imaging pipelines. By enabling high-resolution, multinuclear, and artifact-resistant imaging, PETALUTE supports a new generation of noninvasive tools for tackling global health challenges through earlier diagnosis, treatment monitoring, and mechanistic insight across disease models.
— Uzay Emir, PhD, recently joined the University of North Carolina department of radiology with a joint appointment in the department of biomedical engineering. He is a member of the Biomedical Research Imaging Center as an associate professor from Purdue University.
— Stephen Sawiak, PhD, is a senior research associate and fellow of Fitzwilliam College of the University of Cambridge in the United Kingdom.