Deuterium Metabolic Imaging of Alzheimer Disease at 3-T Magnetic Field Strength: A Pilot Case-Control Study.

Background Impaired glucose metabolism is characteristic of several types of dementia, preceding cognitive symptoms and structural brain changes. Reduced glucose uptake in specific brain regions, detected using fluorine 18 (18F) fluorodeoxyglucose (FDG) PET, is a valuable diagnostic marker in Alzheimer disease (AD). However, the use of 18F-FDG PET in clinical practice may be limited by equipment availability and high cost. Purpose To test the feasibility of using MRI-based deuterium (2H) metabolic imaging (DMI) at a clinical magnetic field strength (3 T) to detect and localize changes in the concentration of glucose and its metabolites in the brains of patients with a clinical diagnosis of AD. Materials and Methods Participants were recruited for this prospective case-control pilot study between March 2021 and February 2023. DMI was performed at 3 T using a custom birdcage head coil following oral administration of deuterium-labeled glucose (0.75 g/kg). Unlocalized whole-brain MR spectroscopy (MRS) and three-dimensional MR spectroscopic imaging (MRSI) (voxel size, 3.2 cm cubic) were performed. Ratios of 2H-glucose, 2H-glutamate and 2H-glutamine (2H-Glx), and 2H-lactate spectroscopic peak signals to 2H-water peak signal were calculated for the whole-brain MR spectra and for individual MRSI voxels. Results A total of 19 participants, including 10 participants with AD (mean age, 68 years ± 5 [SD]; eight males) and nine cognitively healthy control participants (mean age, 70 years ± 6; six males) were evaluated. Whole-brain spectra demonstrated a reduced ratio of 2H-Glx to 2H-glucose peak signals in participants with AD compared with control participants (0.41 ± 0.09 vs 0.58 ± 0.20, respectively; P = .04), suggesting an impairment of oxidative glucose metabolism in AD. However, there was no evidence of localization of these changes to the expected regions of metabolic impairment at MRSI, presumably due to insufficient spatial resolution. Conclusion DMI at 3 T demonstrated impairment of oxidative glucose metabolism in the brains of patients with AD but no evidence of regional signal differences. © RSNA, 2024 Supplemental material is available for this article.

Metabolic imaging across scales reveals distinct prostate cancer phenotypes.

Hyperpolarised magnetic resonance imaging (HP-13C-MRI) has shown promise as a clinical tool for detecting and characterising prostate cancer. Here we use a range of spatially resolved histological techniques to identify the biological mechanisms underpinning differential [1-13C]lactate labelling between benign and malignant prostate, as well as in tumours containing cribriform and non-cribriform Gleason pattern 4 disease. Here we show that elevated hyperpolarised [1-13C]lactate signal in prostate cancer compared to the benign prostate is primarily driven by increased tumour epithelial cell density and vascularity, rather than differences in epithelial lactate concentration between tumour and normal. We also demonstrate that some tumours of the cribriform subtype may lack [1-13C]lactate labelling, which is explained by lower epithelial lactate dehydrogenase expression, higher mitochondrial pyruvate carrier density, and increased lipid abundance compared to lactate-rich non-cribriform lesions. These findings highlight the potential of combining spatial metabolic imaging tools across scales to identify clinically significant metabolic phenotypes in prostate cancer.

23Na MRI: inter-reader reproducibility of normal fibroglandular sodium concentration measurements at 3 T.

BACKGROUND: To study the reproducibility of 23Na magnetic resonance imaging (MRI) measurements from breast tissue in healthy volunteers. METHODS: Using a dual-tuned bilateral 23Na/1H breast coil at 3-T MRI, high-resolution 23Na MRI three-dimensional cones sequences were used to quantify total sodium concentration (TSC) and fluid-attenuated sodium concentration (FASC). B1-corrected TSC and FASC maps were created. Two readers manually measured mean, minimum and maximum TSC and mean FASC values using two sampling methods: large regions of interest (LROIs) and small regions of interest (SROIs) encompassing fibroglandular tissue (FGT) and the highest signal area at the level of the nipple, respectively. The reproducibility of the measurements and correlations between density, age and FGT apparent diffusion coefficient (ADC) values were evaluatedss. RESULTS: Nine healthy volunteers were included. The inter-reader reproducibility of TSC and FASC using SROIs and LROIs was excellent (intraclass coefficient range 0.945-0.979, p < 0.001), except for the minimum TSC LROI measurements (p = 0.369). The mean/minimum LROI TSC and mean LROI FASC values were lower than the respective SROI values (p < 0.001); the maximum LROI TSC values were higher than the SROI TSC values (p = 0.009). TSC correlated inversely with age but not with FGT ADCs. The mean and maximum FGT TSC and FASC values were higher in dense breasts in comparison to non-dense breasts (p < 0.020). CONCLUSIONS: The chosen sampling method and the selected descriptive value affect the measured TSC and FASC values, although the inter-reader reproducibility of the measurements is in general excellent. RELEVANCE STATEMENT: 23Na MRI at 3 T allows the quantification of TSC and FASC sodium concentrations. The sodium measurements should be obtained consistently in a uniform manner. KEY POINTS: • 23Na MRI allows the quantification of total and fluid-attenuated sodium concentrations (TSC/FASC). • Sampling method (large/small region of interest) affects the TSC and FASC values. • Dense breasts have higher TSC and FASC values than non-dense breasts. • The inter-reader reproducibility of TSC and FASC measurements was, in general, excellent. • The results suggest the importance of stratifying the sodium measurements protocol.

Quantitative 23Na magnetic resonance imaging in the abdomen at 3 T.

OBJECTIVES: To assess the feasibility of sodium-23 MRI for performing quantitative and non-invasive measurements of total sodium concentration (TSC) and relaxation in a variety of abdominal organs. MATERIALS AND METHODS: Proton and sodium imaging of the abdomen was performed in 19 healthy volunteers using a 3D cones sequence and a sodium-tuned 4-rung transmit/receive body coil on a clinical 3 T system. The effects of B1 non-uniformity on TSC measurements were corrected using the double-angle method. The long-component of 23Na T2* relaxation time was measured using a series of variable echo-times. RESULTS: The mean and standard deviation of TSC and long-component 23Na T2* values were calculated across the healthy volunteer group in the kidneys, cerebrospinal fluid (CSF), liver, gallbladder, spleen, aorta, and inferior vena cava. DISCUSSION: Mean TSC values in the kidneys, liver, and spleen were similar to those reported using 23Na-MRI previously in the literature. Measurements in the CSF and gallbladder were lower, potentially due to the reduced spatial resolution achievable in a clinically acceptable scan time. Mean long-component 23Na T2* values were consistent with previous reports from the kidneys and CSF. Intra-population standard error was larger in smaller, fluid-filled structures due to fluid motion and partial volume effects.

Current methods for hyperpolarized [1-13C]pyruvate MRI human studies.

MRI with hyperpolarized (HP) 13C agents, also known as HP 13C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of HP agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-13C]pyruvate-by far the most commonly used agent, which sits at a key metabolic junction in glycolysis. The paper is divided into four major topic areas: (1) HP 13C-pyruvate preparation; (2) MRI system setup and calibrations; (3) data acquisition and image reconstruction; and (4) data analysis and quantification. In each area, we identified the key components for a successful study, summarized both published studies and current practices, and discuss evidence gaps, strengths, and limitations. This paper is the output of the "HP 13C MRI Consensus Group" as well as the ISMRM Hyperpolarized Media MR and Hyperpolarized Methods and Equipment study groups. It further aims to provide a comprehensive reference for future consensus, building as the field continues to advance human studies with this metabolic imaging modality.

Imaging tumor lactate is feasible for identifying intermediate-risk prostate cancer patients with postsurgical biochemical recurrence.

While radical prostatectomy remains the mainstay of prostate cancer (PCa) treatment, 20 to 40% of patients develop postsurgical biochemical recurrence (BCR). A particularly challenging clinical cohort includes patients with intermediate-risk disease whose risk stratification would benefit from advanced approaches that complement standard-of-care diagnostic tools. Here, we show that imaging tumor lactate using hyperpolarized 13C MRI and spatial metabolomics identifies BCR-positive patients in two prospective intermediate-risk surgical cohorts. Supported by spatially resolved tissue analysis of established glycolytic biomarkers, this study provides the rationale for multicenter trials of tumor metabolic imaging as an auxiliary tool to support PCa treatment decision-making.

Current Methods for Hyperpolarized [1-13C]pyruvate MRI Human Studies.

MRI with hyperpolarized (HP) 13C agents, also known as HP 13C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of hyperpolarized agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-13C]pyruvate - by far the most commonly used agent, which sits at a key metabolic junction in glycolysis. The paper is divided into four major topic areas: (1) HP 13C-pyruvate preparation, (2) MRI system setup and calibrations, (3) data acquisition and image reconstruction, and (4) data analysis and quantification. In each area, we identified the key components for a successful study, summarized both published studies and current practices, and discuss evidence gaps, strengths, and limitations. This paper is the output of the "HP 13C MRI Consensus Group" as well as the ISMRM Hyperpolarized Media MR and Hyperpolarized Methods & Equipment study groups. It further aims to provide a comprehensive reference for future consensus building as the field continues to advance human studies with this metabolic imaging modality.

The Great Imitator: A Case of Accidental Kratom Overdose.

Kratom (Mitragyna speciosa) is an herb that is sold over the counter in both pill and liquid forms. It contains opioid and stimulant properties and is used for relaxation as well as for weaning off opioid addictions. While a few adverse effects of kratom have been already reported, mainly with concerns around its toxicity, very little is known about it. We report a case of a female in her 40s presenting with signs of hypoxia reversed with naloxone administration, initially suspected to be a case of opioid overdose. Upon becoming alert and oriented, the patient and her husband reported that she consumed a large amount of kratom bought from the local gas station, and he later noticed that her lips were turning blue and she was becoming increasingly altered. Her urine toxicology was noted to be negative for opioids or any other substance use. The patient survived this accidental overdose due to the quick action of her husband, who rushed her to the emergency department (ED) upon realizing she appeared altered and very ill. It is important for emergency medicine practitioners to be aware of kratom overdose as a possible item on the differential diagnosis. This paper focuses on kratom overdose presentation and treatment.

Effectiveness of Hospital-directed Wellness Interventions in COVID-19: A Cross-sectional Survey.

INTRODUCTION: Hospitals have implemented various wellness interventions to offset the negative effects of coronavirus disease 2019 (COVID-19) on emergency physician morale and burnout. There is limited high quality evidence regarding effectiveness of hospital-directed wellness interventions, leaving hospitals without guidance on best practices. We sought to determine intervention effectiveness and frequency of use in the spring/summer 2020. The goal was to facilitate evidence-based guidance for hospital wellness program planning. METHODS: This cross-sectional observational study we used a novel survey tool piloted at a single hospital and then distributed throughout the United States via major emergency medicine (EM) society listservs and closed social media groups. Subjects reported their morale levels using a slider scale from 1 (lowest) to 10 (highest) at the time of the survey and, retrospectively, at their respective COVID-19 peak in 2020. Subjects also rated effectiveness of wellness interventions using a Likert scale from 1 (not at all effective) to 5 (very effective). Subjects indicated their hospital's usage frequency of common wellness interventions. We analyzed results using descriptive statistics and t-tests. RESULTS: Of 76,100 EM society and closed social media group members, 522 (0.69%) subjects were enrolled. Study population demographics were similar to the national emergency physician population. Morale at the time of the survey was worse (mean [M] 4.36, SD 2.29) than the spring/summer 2020 peak (M 4.57, SD 2.13) [t(458)=-2.27, P=0.024]. The most effective interventions were hazard pay (M 3.59, SD 1.12), staff debriefing groups (M 3.51, SD 1.16), and free food (M 3.34, SD 1.14). The most frequently used interventions were free food (350/522, 67.1%), support sign display (300/522, 57.5%), and daily email updates (266/522, 51.0%). Infrequently used were hazard pay (53/522, 10.2%) and staff debriefing groups (127/522, 24.3%). CONCLUSION: There is discordance between the most effective and most frequently used hospital-directed wellness interventions. Only free food was both highly effective and frequently used. Hazard pay and staff debriefing groups were the two most effective interventions but were infrequently used. Daily email updates and support sign display were the most frequently used interventions but were not as effective. Hospitals should focus effort and resources on the most effective wellness interventions.

Implementation of Vertical Split Flow Model for Patient Throughput at a Community Hospital Emergency Department.

BACKGROUND: Hospitals have implemented innovative strategies to address overcrowding by optimizing patient flow through the emergency department (ED). Vertical split flow refers to the concept of assigning patients to vertical chairs instead of horizontal beds based on patient acuity. OBJECTIVE: Evaluate the impact of vertical split flow implementation on ED Emergency Severity Index (ESI) level 3, patient length of stay, and throughput at a community hospital. METHODS: Retrospective cohort study of all ESI level 3 patients presenting to a community hospital ED over a 3-month period prior to and after vertical split flow implementation between 2018 and 2019. RESULTS: In total, data were collected from 10,638 patient visits: 5262 and 5376 patient visits pre- and postintervention, respectively. There was a significant reduction in mean overall length of stay when ESI-3 patients were triaged with vertical split flow (251 min vs 283 min, p < 0.001). CONCLUSIONS: Community hospital ED implementation of vertical split flow for ESI level 3 patients was associated with a significant reduction in overall length of stay and improved throughput. This model provides a solution to increase the number of patients that can be simultaneously cared for in the ED without increasing staffing or physical space.

The use of temozolomide in paediatric metastatic phaeochromocytoma/paraganglioma: A case report and literature review.

There is increasing evidence to support the use of temozolomide therapy for the treatment of metastatic phaeochromocytoma/paraganglioma (PPGL) in adults, particularly in patients with SDHx mutations. In children however, very little data is available. In this report, we present the case of a 12-year-old female with a SDHB-related metastatic paraganglioma treated with surgery followed by temozolomide therapy. The patient presented with symptoms of palpitations, sweating, flushing and hypertension and was diagnosed with a paraganglioma. The primary mass was surgically resected six weeks later after appropriate alpha- and beta-blockade. During the surgery extensive nodal disease was identified that had been masked by the larger paraganglioma. Histological review confirmed a diagnosis of a metastatic SDHB-deficient paraganglioma with nodal involvement. Post-operatively, these nodal lesions demonstrated tracer uptake on 18F-FDG PET-CT. Due to poor tumour tracer uptake on 68Ga-DOTATATE and 123I-MIBG functional imaging studies radionuclide therapy was not undertaken as a potential therapeutic option for this patient. Due to the low tumour burden and lack of clinical symptoms, the multi-disciplinary team opted for close surveillance for the first year, during which time the patient continued to thrive and progress through puberty. 13 months after surgery, evidence of radiological and biochemical progression prompted the decision to start systemic monotherapy using temozolomide. The patient has now completed ten cycles of therapy with limited adverse effects and has benefited from a partial radiological and biochemical response.

Magnetization transfer imaging of ovarian cancer: initial experiences of correlation with tissue cellularity and changes following neoadjuvant chemotherapy.

Objectives: To investigate the relationship between magnetization transfer (MT) imaging and tissue macromolecules in high-grade serous ovarian cancer (HGSOC) and whether MT ratio (MTR) changes following neoadjuvant chemotherapy (NACT). Methods: This was a prospective observational study. 12 HGSOC patients were imaged before treatment. MTR was compared to quantified tissue histology and immunohistochemistry. For a subset of patients (n = 5), MT imaging was repeated after NACT. The Shapiro-Wilk test was used to assess for normality of data and Spearman's rank-order or Pearson's correlation tests were then used to compare MTR with tissue quantifications. The Wilcoxon signed-rank test was used to assess for changes in MTR after treatment. Results: Treatment-naïve tumour MTR was 21.9 ± 3.1% (mean ± S.D.). MTR had a positive correlation with cellularity, rho = 0.56 (p < 0.05) and a negative correlation with tumour volume, ρ = -0.72 (p = 0.01). MTR did not correlate with the extracellular proteins, collagen IV or laminin (p = 0.40 and p = 0.90). For those patients imaged before and after NACT, an increase in MTR was observed in each case with mean MTR 20.6 ± 3.1% (median 21.1) pre-treatment and 25.6 ± 3.4% (median 26.5) post-treatment (p = 0.06). Conclusion: In treatment-naïve HGSOC, MTR is associated with cellularity, possibly reflecting intracellular macromolecular concentration. MT may also detect the HGSOC response to NACT, however larger studies are required to validate this finding. Advances in knowledge: MTR in HGSOC is influenced by cellularity. This may be applied to assess for cell changes following treatment.

Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-13C]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study.

Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (13C) MRI to monitor the exchange of the hyperpolarized 13C label between injected [1-13C]pyruvate and tumor lactate and bicarbonate. Materials and Methods In this prospective study, seven treatment-naive patients (age [mean ± SD], 60 years ± 11; five men) with GBM were imaged at 3 T by using a dual-tuned 13C-hydrogen 1 head coil. Hyperpolarized [1-13C]pyruvate was injected, and signal was acquired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP), and in healthy volunteers by using paired or unpaired t tests and a Wilcoxon signed rank test. The Spearman ρ correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. Results The bicarbonate-to-pyruvate (BP) ratio was lower in the tumor than in the contralateral NABP (P < .01). The tumor lactate-to-pyruvate (LP) ratio was not different from that in the NABP (P = .38). The LP and BP ratios in the NABP were higher than those observed previously in healthy volunteers (P < .05). Tumor lactate and bicarbonate signal intensities were strongly correlated with the pyruvate signal intensity (ρ = 0.92, P < .001, and ρ = 0.66, P < .001, respectively), and the LP ratio was weakly correlated with LDH-A expression in biopsy samples (ρ = 0.43, P = .04). Conclusion Hyperpolarized 13C MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors than in the surrounding NABP. Keywords: Hyperpolarized 13C MRI, Glioblastoma, Metabolism, Cancer, MRI, Neuro-oncology Supplemental material is available for this article. Published under a CC BY 4.0 license.

The potential of hyperpolarised 13C-MRI to target glycolytic tumour core in prostate cancer.

Hyperpolarised [1-13C]pyruvate MRI (HP-13C-MRI) is an emerging metabolic imaging technique that has shown promise for evaluating prostate cancer (PCa) aggressiveness. Accurate tumour delineation on HP-13C-MRI is vital for quantitative assessment of the underlying tissue metabolism. However, there is no consensus on the optimum method for segmenting HP-13C-MRI, and whole-mount pathology (WMP) as the histopathological gold-standard is only available for surgical patients. Although proton MRI can be used for tumour delineation, this approach significantly underestimates tumour volume, and metabolic tumour segmentation based on HP-13C-MRI could provide an important functional metric of tumour volume. In this study, we quantified metabolism using HP-13C-MRI and segmentation approaches based on WMP maps, 1H-MRI-derived T2-weighted imaging (T2WI), and HP-13C-MRI-derived total carbon signal-to-noise ratio maps (TC-SNR) with an SNR threshold of 5.0. 13C-labelled pyruvate SNR, lactate SNR, TC-SNR, and the pyruvate-to-lactate exchange rate constant (kPL) were significantly higher when measured using the TC-SNR-guided approach, which also corresponded to a significantly higher tumour epithelial expression on RNAscope imaging of the enzyme catalysing pyruvate-to-lactate metabolism (lactate dehydrogenase (LDH)). However, linear regression and Bland-Altman analyses demonstrated a strong linear relationship between all three segmentation approaches, which correlated significantly with RNA-scope-derived epithelial LDH expression. These results suggest that standard-of-care T2WI and TC-SNR maps could be used as clinical reference tools for segmenting localised PCa on HP-13C-MRI in the absence of the WMP gold standard. The TC-SNR-guided approach could be used clinically to target biopsies towards highly glycolytic tumour areas and therefore to sample aggressive disease with higher precision. KEY POINTS: • T2WI- and TC-SNR-guided segmentations can be used in all PCa patients and do not explicitly require WMP maps. • Agreement between the three segmentation approaches is biologically validated by their strong relationship with epithelial LDH mRNA expression. • The TC-SNR-guided approach can potentially be used to identify occult disease on 1H-MRI and target the most glycolytically active regions.

Increased Asymmetric Perfusion of the Cerebral Cortices and Thalamus Indicates Individuals at Risk for Bipolar Disorder: A Family Cohort Single Photon Emission Computed Tomography Neuroimaging Study.

Bipolar disorder is a significant mental illness affecting over 4 million people in North America and approximately 46 million worldwide. While the onset of bipolar disorder is typically in late adolescence and early adulthood, the correct diagnosis can be delayed for several years. This delay can result in inappropriate pharmaceutical interventions, loss of career or productivity, suicide, family hardship, and unnecessary expense. Moreover, prolonged untreated or inappropriately treated bipolar disorder may cause damage to the brain. Early diagnosis is a critical need to circumvent the damage, suffering, and expense caused by the current delay. Brain perfusion single photon emission computed tomography (SPECT) neuroimaging reveals visual correlates of brain function. Herein, a family cohort all with bipolar disorder is described and their symptoms correlated with findings on the individual SPECT brain scans. The family consisted of two parents and three children (one female). The scans were interpreted by a panel of experts. Then a post hoc region-of-interest (ROI) analysis was conducted on SPECT data normalized to the cerebellum maximum with comparison to similarly normalized data from a normative sample. These findings support two distinct patterns of SPECT perfusion scan changes that can be found in individuals with bipolar disorder. In addition, these findings indicate that SPECT scan findings may be predictive of individual risk for progressing to symptomatic bipolar disorder. While preliminary, the findings in this cohort support the need for larger, diverse cohort studies of bipolar and control subjects to assess the predictive value of these particular SPECT perfusion findings in bipolar disorder.

Using Single-Photon Emission Computerized Tomography on Patients With Positive Quantitative Electroencephalogram to Evaluate Chronic Mild Traumatic Brain Injury With Persistent Symptoms.

Background: Following mild traumatic brain injury (mTBI), also known as concussion, many patients with chronic symptoms (>3 months post injury) receive conventional imaging such as computed tomography (CT) or magnetic resonance imaging (MRI). However, these modalities often do not show changes after mTBI. We studied the benefit of triaging patients with ongoing symptoms >3 months post injury by quantitative electroencephalography (qEEG) and then completing a brain single positron emission computed tomography (SPECT) to aid in diagnosis and early detection of brain changes. Methods: We conducted a retrospective case review of 30 outpatients with mTBI. The patients were assessed by a neurologist, consented, and received a qEEG, and if the qEEG was positive, they consented and received a brain SPECT scan. The cases and diagnostic tools were collectively reviewed by a multidisciplinary group of physicians in biweekly team meetings including neurology, nuclear medicine, psychiatry, neuropsychiatry, general practice psychotherapy, neuro-ophthalmology, and chiropractic providers. The team noted the cause of injury, post injury symptoms, relevant past medical history, physical examination findings, and diagnoses, and commented on patients' SPECT scans. We then analyzed the SPECT scans quantitatively using the 3D-SSP software. Results: All the patients had cerebral perfusion abnormalities demonstrated by SPECT that were mostly undetectable by conventional imaging (CT/MRI). Perfusion changes were localized primarily in the cerebral cortex, basal ganglia, and cingulate cortex, and correlated with the patients' symptoms and examination findings. Qualitative and quantitative analyses yielded similar results. Most commonly, the patients experienced persistent headache, memory loss, concentration difficulties, depression, and cognitive impairment post mTBI. Because of their symptoms, most of the patients were unable to return to their previous employment and activity level. Conclusion: Our findings outline the physical basis of neurological and psychiatric symptoms experienced by patients with mTBI. Increased detection of mTBI can lead to development of improved targeted treatments for mTBI and its various sequelae.

Deuterium metabolic imaging and hyperpolarized 13C-MRI of the normal human brain at clinical field strength reveals differential cerebral metabolism.

Deuterium metabolic imaging (DMI) and hyperpolarized 13C-pyruvate MRI (13C-HPMRI) are two emerging methods for non-invasive and non-ionizing imaging of tissue metabolism. Imaging cerebral metabolism has potential applications in cancer, neurodegeneration, multiple sclerosis, traumatic brain injury, stroke, and inborn errors of metabolism. Here we directly compare these two non-invasive methods at 3 T for the first time in humans and show how they simultaneously probe both oxidative and non-oxidative metabolism. DMI was undertaken 1-2 h after oral administration of [6,6'-2H2]glucose, and 13C-MRI was performed immediately following intravenous injection of hyperpolarized [1-13C]pyruvate in ten and nine normal volunteers within each arm respectively. DMI was used to generate maps of deuterium-labelled water, glucose, lactate, and glutamate/glutamine (Glx) and the spectral separation demonstrated that DMI is feasible at 3 T. 13C-HPMRI generated maps of hyperpolarized carbon-13 labelled pyruvate, lactate, and bicarbonate. The ratio of 13C-lactate/13C-bicarbonate (mean 3.7 ± 1.2) acquired with 13C-HPMRI was higher than the equivalent 2H-lactate/2H-Glx ratio (mean 0.18 ± 0.09) acquired using DMI. These differences can be explained by the route of administering each probe, the timing of imaging after ingestion or injection, as well as the biological differences in cerebral uptake and cellular physiology between the two molecules. The results demonstrate these two metabolic imaging methods provide different yet complementary readouts of oxidative and reductive metabolism within a clinically feasible timescale. Furthermore, as DMI was undertaken at a clinical field strength within a ten-minute scan time, it demonstrates its potential as a routine clinical tool in the future.

Sodium accumulation in breast cancer predicts malignancy and treatment response.

BACKGROUND: Breast cancer remains a leading cause of death in women and novel imaging biomarkers are urgently required. Here, we demonstrate the diagnostic and treatment-monitoring potential of non-invasive sodium (23Na) MRI in preclinical models of breast cancer. METHODS: Female Rag2-/- Il2rg-/- and Balb/c mice bearing orthotopic breast tumours (MDA-MB-231, EMT6 and 4T1) underwent MRI as part of a randomised, controlled, interventional study. Tumour biology was probed using ex vivo fluorescence microscopy and electrophysiology. RESULTS: 23Na MRI revealed elevated sodium concentration ([Na+]) in tumours vs non-tumour regions. Complementary proton-based diffusion-weighted imaging (DWI) linked elevated tumour [Na+] to increased cellularity. Combining 23Na MRI and DWI measurements enabled superior classification accuracy of tumour vs non-tumour regions compared with either parameter alone. Ex vivo assessment of isolated tumour slices confirmed elevated intracellular [Na+] ([Na+]i); extracellular [Na+] ([Na+]e) remained unchanged. Treatment with specific inward Na+ conductance inhibitors (cariporide, eslicarbazepine acetate) did not affect tumour [Na+]. Nonetheless, effective treatment with docetaxel reduced tumour [Na+], whereas DWI measures were unchanged. CONCLUSIONS: Orthotopic breast cancer models exhibit elevated tumour [Na+] that is driven by aberrantly elevated [Na+]i. Moreover, 23Na MRI enhances the diagnostic capability of DWI and represents a novel, non-invasive biomarker of treatment response with superior sensitivity compared to DWI alone.

Longitudinal Single Photon Emission Computed Tomography Neuroimaging as an Indication of Improvement in Psychiatric Disorders in a Community Psychiatric Practice.

In the community, there is a need to more objectively evaluate the response of common chronic psychiatric disorders to treatment. Brain single photon emission computed tomography (SPECT) indirectly measures cerebral functional activity by uptake of a radiotracer, which follows regional cerebral blood flow. Brain 3D Thresholded SPECT scans are thresholded three dimensional images derived from brain SPECT data. A retrospective community study of longitudinal (before and after treatment) brain 3D Thresholded SPECT scans of 73 patients with all-cause psychiatric disorders (most frequent diagnostic clusters: attention-deficit hyperactivity disorder, post-mild traumatic brain injury, affective disorders, psychotic disorders, post-viral chronic syndromes), shows these baseline SPECT scans predict improvement (non-worsening to large improvement) in clinical functioning with a sensitivity of 94% (95% confidence interval 86-98%) and a specificity of 67% (95% confidence interval 21-94%). In contrast, contemporaneous analysis by the same radiologist of conventional 2D reading of the same before and after treatment brain SPECT scan data of the same 73 patients, predicted improvement (non-worsening to large improvement) in clinical functioning with a sensitivity of only 26% (95% confidence interval 17-37%) although with a specificity of 100% (95% confidence interval 44-100%). These data suggest 3D Thresholded SPECT scans can provide the clinician with a more objective measure for verifying improvement in psychiatric disorders seen in the community, consistent with prior studies of SPECT as a measure of neurobiological change. Furthermore, these data suggest 3D Thresholded SPECT scans may have clinical application in guiding treatment and potentially improving outcomes.