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Lucas Carvajal

Bio: Lucas Carvajal is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Imaging phantom & Magnetic resonance imaging. The author has an hindex of 17, co-authored 27 publications receiving 1927 citations.

Papers
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Journal ArticleDOI
TL;DR: This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-13C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer and showed elevated levels of lactate, alanine, and bicarbonate in regions of biopsy-proven cancer.
Abstract: This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-13C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo 13C MR data, it is possible to evaluate the distribution of agents such as [1-13C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds. Preclinical studies in cancer models have detected elevated levels of hyperpolarized [1-13C]lactate in tumor, with the ratio of [1-13C]lactate/[1-13C]pyruvate being increased in high-grade tumors and decreased after successful treatment. Translation of this technology into humans was achieved by modifying the instrument that generates the hyperpolarized agent, constructing specialized radio frequency coils to detect 13C nuclei, and developing new pulse sequences to efficiently capture the signal. The study population comprised patients with biopsy-proven prostate cancer, with 31 subjects being injected with hyperpolarized [1-13C]pyruvate. The median time to deliver the agent was 66 s, and uptake was observed about 20 s after injection. No dose-limiting toxicities were observed, and the highest dose (0.43 ml/kg of 230 mM agent) gave the best signal-to-noise ratio for hyperpolarized [1-13C]pyruvate. The results were extremely promising in not only confirming the safety of the agent but also showing elevated [1-13C]lactate/[1-13C]pyruvate in regions of biopsy-proven cancer. These findings will be valuable for noninvasive cancer diagnosis and treatment monitoring in future clinical trials.

1,054 citations

Journal ArticleDOI
TL;DR: The purpose of this study was to quantify local field shifts in MS and to investigate their relation to disease duration and disability status.
Abstract: Objective Magnetic resonance imaging at 7 Tesla produces high-resolution gradient-echo phase images of patients with multiple sclerosis (MS) that quantify the local field shifts from iron in the basal ganglia and lesions. Phase imaging is easily integrated into clinical examinations because it is a postprocessing technique and does not require additional scanning. The purpose of this study was to quantify local field shifts in MS and to investigate their relation to disease duration and disability status. Methods Thirty-two subjects including 19 patients with MS and 13 age- and sex-matched control subjects were scanned at a spatial resolution of up to 195 × 260μm. Data were postprocessed to produce anatomical quantitative phase images of local field shifts, as well as conventional magnitude images. Results The phase images showed an increased local field in the caudate, putamen, and globus pallidus of patients relative to control subjects (p < 0.01). The local field in the caudate was strongly correlated with disease duration (r2 = 0.77; p < 0.001). Phase images showed contrast in 74% of the 403 lesions, increasing the total lesion count by more than 30% and showing distinct peripheral rings and a close association with vasculature. Interpretation The increased field in the basal ganglia and correlation with disease duration suggest pathological iron content increases in MS. The peripheral phase rings are consistent with histological data demonstrating iron-rich macrophages at the periphery of a subset of lesions. The clearly defined vessels penetrating MS lesions should increase our ability to detect focal vascular abnormalities specifically related to demyelinating processes. Ann Neurol 2008;64:707–713

256 citations

Journal ArticleDOI
TL;DR: The purpose of this study was to develop and implement experimental strategies for using [1‐13C]pyruvate to probe in vivo metabolism for patients with brain tumors and other neurological diseases.
Abstract: Author(s): Park, Ilwoo; Larson, Peder EZ; Gordon, Jeremy W; Carvajal, Lucas; Chen, Hsin-Yu; Bok, Robert; Van Criekinge, Mark; Ferrone, Marcus; Slater, James B; Xu, Duan; Kurhanewicz, John; Vigneron, Daniel B; Chang, Susan; Nelson, Sarah J | Abstract: Purpose: Hyperpolarized carbon-13 (13C) metabolic imaging is a noninvasive imaging modality for evaluating real-time metabolism. The purpose of this study was to develop and implement experimental strategies for using [1-13C]pyruvate to probe in vivo metabolism for patients with brain tumors and other neurological diseases. Methods: The 13C radiofrequency coils and pulse sequences were tested in a phantom and were performed using a 3 Tesla whole-body scanner. Samples of [1-13C]pyruvate were polarized using a SPINlab system. Dynamic 13C data were acquired from 8 patients previously diagnosed with brain tumors, who had received treatment and were being followed with serial magnetic resonance scans. Results: The phantom studies produced good-quality spectra with a reduction in signal intensity in the center attributed to the reception profiles of the 13C receive coils. Dynamic data obtained from a 3-cm slice through a patient's brain following injection with [1-13C]pyruvate showed the anticipated arrival of the agent, its conversion to lactate and bicarbonate, and subsequent reduction in signal intensity. A similar temporal pattern was observed in 2D dynamic patient studies, with signals corresponding to pyruvate, lactate, and bicarbonate being in normal appearing brain, but only pyruvate and lactate being detected in regions corresponding to the anatomical lesion. Physiological monitoring and follow-up confirmed that there were no adverse events associated with the injection. Conclusion: This study has presented the first application of hyperpolarized 13C metabolic imaging in patients with brain tumor and demonstrated the safety and feasibility of using hyperpolarized [1-13C]pyruvate to evaluate in vivo brain metabolism. Magn Reson Med 80:864–873, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

123 citations

Journal ArticleDOI
TL;DR: In this paper, the authors developed optimized high-resolution 7T MRI techniques using high sensitivity, specialized phasedarray coils, for improved gray matter (GM) and white matter differentiation, in an effort to improve visualization of multiple sclerosis (MS) lesions in vivo.
Abstract: Recent advancement for magnetic resonance imaging (MRI) involves the incorporation of higher-field strengths. Although imagers with higher magnetic field strengths were developed and tested in research labs, the direct application to patient MR studies have been extremely limited. Imaging at 7 Tesla (7T) affords advantages in signal-to-noise ratio and image contrast and resolution; however, these benefits can only be realized if the correct coils exist to capture the images. The objective of this study was to develop optimized high-resolution 7T MRI techniques using high sensitivity, specialized phased-array coils, for improved gray matter (GM) and white matter differentiation, in an effort to improve visualization of multiple sclerosis (MS) lesions in vivo. Twenty-three subjects were enrolled in this preliminary study, 17 with clinically definite MS (11 females, 6 males; mean age 43.4 years; range 22-64 years) and 6 healthy controls (2 females, 4 males; mean age 39.0 years; range 27-67 years). MR imaging of MS patients at 7T was demonstrated to be safe, well tolerated, and provided high-resolution anatomical images allowing visualization of structural abnormalities localized near or within the cortical layers. Clear involvement of the GM was observed with improved morphological detail in comparison to imaging at lower-field strength.

77 citations

Journal ArticleDOI
TL;DR: It is shown that bSSFP and spin‐echo imaging is possible at higher field strengths within 3.2 W/kg specific absorption rate (SAR) constraints and there is SNR benefit and great potential for bone and cartilage imaging atHigher field strength.
Abstract: The purpose of this work was to investigated the feasibility of fully-balanced steady-state free-precession (bSSFP) pulse sequence for trabecular bone and knee cartilage imaging in vivo using ultra-high-field (UHF) MRI at 7T in comparison with pulse sequences previously used at 3T. We showed that bSSFP and spin-echo imaging is possible at higher field strengths within 3.2 W/kg specific absorption rate (SAR) constraints. All pulse sequences were numerically optimized based on measured tissue relaxation parameters from six healthy volunteers (T1 = 820 ± 128 ms, T2 = 43.5 ± 3 ms for bone marrow and T1 = 1745 ± 104 ms and T2 = 30 ± 4 ms for cartilage). From simulations of the Bloch equation, a signal-to-noise ratio (SNR) increase of more than 1.9 was predicted. Cartilage SNR of bSSFP was 2.4 times higher at 7T (51.3 ± 4.3) compared with 3T (21.3 ± 3.3). Bone SNR increased from 11.8 ± 2.0 to 13.2 ± 2.5 at the higher field strength. We concluded that there is SNR benefit and great potential for bone and cartilage imaging at higher field strength. Magn Reson Med, 2007. © 2007 Wiley-Liss, Inc.

62 citations


Cited by
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Journal ArticleDOI
TL;DR: These revisions simplify the McDonald Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.
Abstract: New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.

8,883 citations

Journal ArticleDOI
09 Feb 2017-Cell
TL;DR: In this paper, the authors define pathways that are limiting for cancer progression and understand the context specificity of metabolic preferences and liabilities in malignant cells, which can guide the more effective targeting of metabolism to help patients.

1,427 citations

Journal ArticleDOI
TL;DR: MRI can often identify changes in iron homoeostasis, thus providing a potential diagnostic biomarker of neurodegenerative diseases and an important avenue to reduce iron accumulation is the use of iron chelators that are able to cross the blood-brain barrier, penetrate cells, and reduce excessive iron accumulation, thereby affording neuroprotection.
Abstract: Summary In the CNS, iron in several proteins is involved in many important processes such as oxygen transportation, oxidative phosphorylation, myelin production, and the synthesis and metabolism of neurotransmitters. Abnormal iron homoeostasis can induce cellular damage through hydroxyl radical production, which can cause the oxidation and modification of lipids, proteins, carbohydrates, and DNA. During ageing, different iron complexes accumulate in brain regions associated with motor and cognitive impairment. In various neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, changes in iron homoeostasis result in altered cellular iron distribution and accumulation. MRI can often identify these changes, thus providing a potential diagnostic biomarker of neurodegenerative diseases. An important avenue to reduce iron accumulation is the use of iron chelators that are able to cross the blood–brain barrier, penetrate cells, and reduce excessive iron accumulation, thereby affording neuroprotection.

1,089 citations

Journal ArticleDOI
TL;DR: This comprehensive review describes the state of the art of clinically approved contrast agents, their mechanism of action, and factors influencing their safety and efforts to make safer contrast agents either by increasing relaxivity, increasing resistance to metal ion release, or by moving to gadolinium(III)-free alternatives.
Abstract: Tens of millions of contrast-enhanced magnetic resonance imaging (MRI) exams are performed annually around the world. The contrast agents, which improve diagnostic accuracy, are almost exclusively small, hydrophilic gadolinium(III) based chelates. In recent years concerns have arisen surrounding the long-term safety of these compounds, and this has spurred research into alternatives. There has also been a push to develop new molecularly targeted contrast agents or agents that can sense pathological changes in the local environment. This comprehensive review describes the state of the art of clinically approved contrast agents, their mechanism of action, and factors influencing their safety. From there we describe different mechanisms of generating MR image contrast such as relaxation, chemical exchange saturation transfer, and direct detection and the types of molecules that are effective for these purposes. Next we describe efforts to make safer contrast agents either by increasing relaxivity, increasing resistance to metal ion release, or by moving to gadolinium(III)-free alternatives. Finally we survey approaches to make contrast agents more specific for pathology either by direct biochemical targeting or by the design of responsive or activatable contrast agents.

817 citations

Journal ArticleDOI
TL;DR: The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism as discussed by the authors, which shares reactions with the Entner-Doudoroff pathway and the Calvin cycle and divides into an oxidative and non-oxidative branch.
Abstract: The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism. The PPP is important to maintain carbon homoeostasis, to provide precursors for nucleotide and amino acid biosynthesis, to provide reducing molecules for anabolism, and to defeat oxidative stress. The PPP shares reactions with the Entner-Doudoroff pathway and Calvin cycle and divides into an oxidative and non-oxidative branch. The oxidative branch is highly active in most eukaryotes and converts glucose 6-phosphate into carbon dioxide, ribulose 5-phosphate and NADPH. The latter function is critical to maintain redox balance under stress situations, when cells proliferate rapidly, in ageing, and for the 'Warburg effect' of cancer cells. The non-oxidative branch instead is virtually ubiquitous, and metabolizes the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate as well as sedoheptulose sugars, yielding ribose 5-phosphate for the synthesis of nucleic acids and sugar phosphate precursors for the synthesis of amino acids. Whereas the oxidative PPP is considered unidirectional, the non-oxidative branch can supply glycolysis with intermediates derived from ribose 5-phosphate and vice versa, depending on the biochemical demand. These functions require dynamic regulation of the PPP pathway that is achieved through hierarchical interactions between transcriptome, proteome and metabolome. Consequently, the biochemistry and regulation of this pathway, while still unresolved in many cases, are archetypal for the dynamics of the metabolic network of the cell. In this comprehensive article we review seminal work that led to the discovery and description of the pathway that date back now for 80 years, and address recent results about genetic and metabolic mechanisms that regulate its activity. These biochemical principles are discussed in the context of PPP deficiencies causing metabolic disease and the role of this pathway in biotechnology, bacterial and parasite infections, neurons, stem cell potency and cancer metabolism.

817 citations