Hyperpolarized- 13 C magnetic resonance imaging (HP- 13 C MRI) was used to image changes in 13 C-lactate signal during a visual stimulus condition in comparison to an eyes-closed control condition. Whole-brain 13 C-pyruvate, 13 C-lactate and 13 C-bicarbonate production was imaged in healthy volunteers (N=6, ages 24-33) for the two conditions using two separate hyperpolarized 13 C-pyruvate injections. BOLD-fMRI scans were used to delineate regions of functional activation. 13 C-metabolite signal was normalized by 13 C-metabolite signal from the brainstem and the percentage change in 13 C-metabolite signal conditions was calculated. A one-way Wilcoxon signed-rank test showed a significant increase in 13 C-lactate in regions of activation when compared to the remainder of the brain ( p = 0.02, V = 21). No significant increase was observed in 13 C-pyruvate ( p = 0.11, V = 17) or 13 C-bicarbonate ( p = 0.95, V = 3) signal. The results show an increase in 13 C-lactate production in the activated region that is measurable with HP- 13 C MRI.

Background Stereotactic radiosurgery (SRS) for the treatment of brain metastases delivers a high dose of radiation with excellent local control but comes with the risk of radiation necrosis (RN), which can be difficult to distinguish from tumor progression (TP). Magnetization transfer (MT) and chemical exchange saturation transfer (CEST) are promising techniques for distinguishing RN from TP in brain metastases. Previous studies used a 2D continuous-wave (ie, block radiofrequency [RF] saturation) MT/CEST approach. The purpose of this study is to investigate a 3D pulsed saturation MT/CEST approach with perfusion MRI for distinguishing RN from TP in brain metastases.Methods The study included 73 patients scanned with MT/CEST MRI previously treated with SRS or fractionated SRS who developed enhancing lesions with uncertain diagnoses of RN or TP. Perfusion MRI was acquired in 49 of 73 patients. Clinical outcomes were determined by at least 6 months of follow-up or via pathologic confirmation (in 20% of the lesions).Results Univariable logistic regression resulted in significant variables of the quantitative MT parameter 1/(RAT2A), with 5.9 +/- 2.7 for RN and 6.5 +/- 2.9 for TP. The highest AUC of 75% was obtained using a multivariable logistic regression model for MT/CEST parameters, which included the CEST parameters of AREXAmide,0.625 mu T (P = .013), AREXNOE,0.625 mu T (P = .008), 1/(RAT2A) (P = .004), and T1 (P = .004). The perfusion rCBV parameter did not reach significance.Conclusions Pulsed saturation transfer was sufficient for achieving a multivariable AUC of 75% for differentiating between RN and TP in brain metastases, but had lower AUCs compared to previous studies that used a block RF approach.

PURPOSE:To test the hypothesis that lactate oxidation contributes to the   13 $$ {}^{13} $$ C-bicarbonate signal observed in the awake human brain using hyperpolarized   13 $$ {}^{13} $$ C MRI. METHODS:Healthy human volunteers (N = 6) were scanned twice using hyperpolarized   13 $$ {}^{13} $$ C-MRI, with increased radiofrequency saturation of   13 $$ {}^{13} $$ C-lactate on one set of scans.   13 $$ {}^{13} $$ C-lactate,   13 $$ {}^{13} $$ C-bicarbonate, and   13 $$ {}^{13} $$ C-pyruvate signals for 132 brain regions across each set of scans were compared using a clustered Wilcoxon signed-rank test. RESULTS:Increased   13 $$ {}^{13} $$ C-lactate radiofrequency saturation resulted in a significantly lower   13 $$ {}^{13} $$ C-bicarbonate signal (p = 0.04). These changes were observed across the majority of brain regions. CONCLUSION:Radiofrequency saturation of   13 $$ {}^{13} $$ C-lactate leads to a decrease in   13 $$ {}^{13} $$ C-bicarbonate signal, demonstrating that the   13 $$ {}^{13} $$ C-lactate generated from the injected   13 $$ {}^{13} $$ C-pyruvate is being converted back to   13 $$ {}^{13} $$ C-pyruvate and oxidized throughout the human brain.

Purpose: To test the hypothesis that lactate oxidation contributes to the (13)13 C-bicarbonate signal observed in the awake human brain using hyperpolarized (13)13 C MRI.Methods: Healthy human volunteers (N = 6) were scanned twice using hyperpolarized (13)13 C-MRI, with increased radiofrequency saturation of (13)13 C-lactate on one set of scans. (13)13 C-lactate, (13)13 C-bicarbonate, and (13)13 C-pyruvate signals for 132 brain regions across each set of scans were compared using a clustered Wilcoxon signed-rank test.Results: Increased (13)13 C-lactate radiofrequency saturation resulted in a significantly lower (13)13 C-bicarbonate signal (p = 0.04). These changes were observed across the majority of brain regions.Conclusion: Radiofrequency saturation of (13)13 C-lactate leads to a decrease in (13)13 C-bicarbonate signal, demonstrating that the (13)13 C-lactate generated from the injected (13)13 C-pyruvate is being converted back to (13)13 C-pyruvate and oxidized throughout the human brain.

Purpose To test the hypothesis that lactate shuttling contributes to the 13 C-lactate and 13 C-bicarbonate signal observed in the awake human brain using hyperpolarized 13 C MRI. Methods Healthy human volunteers (n = 6) were scanned twice using hyperpolarized 13 C-MRI, with reduced radiofrequency saturation of 13 C-lactate on one set of scans. 13 C-lactate, 13 C-bicarbonate, and 13 C-pyruvate signals for 132 brain regions across each set of scans were compared using a clustered Wilcoxon sum rank test. Results Reduced 13 C-lactate radiofrequency saturation resulted in a significantly greater 13 C-bicarbonate signal ( p = 0.04). These changes were observed across the majority of brain regions. Conclusion Radiofrequency saturation of 13 C-lactate leads to a decrease in 13 C-bicarbonate signal, demonstrating that the 13 C-lactate generated from the injected 13 C-pyruvate is being converted back to 13 C-pyruvate and oxidized throughout the human brain.

It is well known that glucose is the primary source of energy in the brain, but mounting evidence suggests that at least some of this glucose is first converted to lactate and shuttled between cellular compartments before being oxidized in the TCA cycle. In this study, the hypothesis that this ”lactate shuttle” contributes to the 13 C-lactate and 13 C-bicarbonate signal observed in the awake human brain is tested using hyperpolarized 13 C MRI (HP 13 C-MRI).

In this study, hyperpolarized C-13 MRI (HP-C-13 MRI) was used to investigate changes in the uptake and metabolism of pyruvate with age. Hyperpolarized C-13-pyruvate was administered to healthy aging individuals (N = 35, ages 21-77) and whole-brain spatial distributions of C-13-lactate and C-13-bicarbonate production were measured. Linear mixed-effects regressions were performed to compute the regional percentage change per decade, showing a significant reduction in both normalized C-13-lactate and normalized C-13-bicarbonate production with age: -7%+/- 2%$$ -7\%\pm 2\% $$ per decade for C-13-lactate and -9%+/- 4%$$ -9\%\pm 4\% $$ per decade for C-13-bicarbonate. Certain regions, such as the right medial precentral gyrus, showed greater rates of change while the left caudate nucleus had a flat C-13-lactate versus age and a slightly increasing C-13-bicarbonate versus age. The results show that both the production of lactate (visible as C-13-lactate signal) as well as the consumption of monocarboxylates to make acetyl-CoA (visible as C-13-bicarbonate signal) decrease with age and that the rate of change varies by brain region.

Brain metastases are increasingly being treated with stereotactic radiosurgery; however, 20-30% of treated tumors recur locally post-treatment. Hyperpolarized [1- 13 C]pyruvate magnetic resonance imaging (HP 13 C MRI) is an emerging metabolic imaging modality that measures key metabolic phenotypes indicative of tumor biology. Here we investigate pre-treatment [1- 13 C]pyruvate uptake – a potential marker of monocarboxylate transporter 1 expression and tumor vascularity – via HP 13 C MR images as a predictor of local recurrence. [1- 13 C]pyruvate uptake establishes a robust predictive model (AUC = 0.73) and, as a result, can inform treatment decisions should the model predict a non-response to SRS.

Research imaging in healthy and clinical youth populations yields incidental findings that require a management strategy. Our primary objective was to document the frequency and nature of incidental findings within a research group integrating multiple imaging modalities. A second objective was to describe the evolution of an approach to handling incidental findings. A case example was included to display the intricacies of some of these scenarios. Youth, ages 13-20 years, with bipolar disorder, familial risk for bipolar disorder, or healthy controls, obtained one or a combination of neuroimaging, cardio-thoracic imaging, retinal imaging, and carotid imaging. All images were systematically reviewed for incidental findings. Overall, of 223 participants (n = 102 healthy controls), 59% (n = 131) had a brain magnetic resonance imaging (MRI) incidental finding and 27% (n = 60) had at least one incidental brain finding requiring non-urgent follow-up. In addition, of 109 participants with chest/cardiac MRI and carotid ultrasound, 3% (n = 3) had chest findings, 2% (n = 2) had cardiac findings, and 1% (n = 1) had a carotid finding. Of 165 youth with retinal imaging, 1% (n = 2) had incidental findings. While the vast majority of these incidental findings were of a non-serious, non-urgent nature, there were noteworthy exceptions. Imaging research groups need a system that emphasizes the value of clinical review of research images and one that is collaborative and responsive in order to inform follow-up plans. Rating systems that have been developed and used in neuroimaging for the classification of incidental findings can be adapted for use in areas other than the brain. Regardless of severity, incidental findings may raise anxiety in youth participants and their parents. The optimal threshold is one that balances transparency with utility.

Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a significant fraction of patients. Local progression after SRS can often only be detected with increased volume of enhancement on serial MRI scans which may lag true progression by weeks or months. Patients with intracranial metastases (N = 11) were scanned using hyperpolarized $$^{13}$$ C MRI prior to treatment with stereotactic radiosurgery (SRS). The status of each lesion was then recorded at six months post-treatment follow-up (or at the time of death). The positive predictive value of $$^{13}$$ C-lactate signal, measured pre-treatment, for prediction of progression of intracranial metastases at six months post-treatment with SRS was 0.8 $$p < 0.05$$ , and the AUC from an ROC analysis was 0.77 $$p < 0.05$$ . The distribution of $$^{13}$$ C-lactate z-scores was different for intracranial metastases from different primary cancer types (F = 2.46, $$p = 0.1$$ ). Hyperpolarized $$^{13}$$ C imaging has potential as a method for improving outcomes for patients with intracranial metastases, by identifying patients at high risk of treatment failure with SRS and considering other therapeutic options such as surgery.

Background Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a significant fraction of patients. Local progression after SRS can often only be detected with increased volume of enhancement on serial MRI scans which may lag true progression by weeks or months. Methods Patients with intracranial metastases (N = 11) were scanned using hyperpolarized ^13 C MRI prior to treatment with stereotactic radiosurgery (SRS). The status of each lesion was then recorded at six months post-treatment follow-up (or at the time of death). Results The positive predictive value of ^13 C-lactate signal, measured pre-treatment, for prediction of progression of intracranial metastases at six months post-treatment with SRS was 0.8 p < 0.05 , and the AUC from an ROC analysis was 0.77 p < 0.05 . The distribution of ^13 C-lactate z -scores was different for intracranial metastases from different primary cancer types (F = 2.46, p = 0.1 ). Conclusions Hyperpolarized ^13 C imaging has potential as a method for improving outcomes for patients with intracranial metastases, by identifying patients at high risk of treatment failure with SRS and considering other therapeutic options such as surgery.

Lactate is now recognized as an important intermediate in brain metabolism, but its role is still under investigation. In this work we mapped the distribution of lactate and bicarbonate produced from intravenously injected 13C-pyruvate over the whole brain using a new imaging method, hyperpolarized 13C MRI (N = 14, ages 23 to 77). Segmenting the 13C-lactate images into brain atlas regions revealed a pattern of lactate that was preserved across individuals. Higher lactate signal was observed in cortical grey matter compared to white matter and was highest in the precuneus, cuneus and lingual gyrus. Bicarbonate signal, indicating flux of [1–13C]pyruvate into the TCA cycle, also displayed consistent spatial distribution. One-way ANOVA to test for significant differences in lactate among atlas regions gave F = 87.6 and p < 10−6. This report of a “lactate topography” in the human brain and its consistent pattern is evidence of region-specific lactate biology that is preserved across individuals.

Axial T1 projection showing the relation of VIM target 3 mm medial and anterior to pyramidal tract and medial lemniscus respectively

Osteoid osteoma (OO), a small painful benign bone tumor, is the most common bone tumor in children. Pain is managed with nonsteroidal anti-inflammatory drugs but minimally invasive techniques, such as CT-guided laser ablation, have become a standard intervention. However, the potential for non-target injury is a concern as tissue temperature cannot be measured with CT and the laser induces temperatures >90°C for 10 minutes. It also includes risks from exposure to ionizing radiation, fracture, infection and transmitted thermal damage from the access needle. Magnetic resonance guided high intensity focused ultrasound (MRgHIFU) has been used successfully in small cohorts of adults with OO. The noninvasive nature of the energy means that procedures do not need to be conducted in a sterile environment since there is no mechanical penetration of the bone, reducing the chance of pathologic fracture and infection.

Breast cancer is the most common life-threatening malignancy in women. Predicting a patient’s response to neoadjuvant, or preoperative, chemotherapy is difficult. Because standard mammographic procedures do not accurately measure changes in tumour volume, monitoring response is usually repeated on a 3-6 month interval. For patients with an aggressive disease, this time frame may lead to months of ineffective therapy, permanent and irreversible losses in quality of life and early mortality. Thus an early, noninvasive and reproducible method to determine a tumour’s responsiveness to a particular therapy would greatly benefit these patients. Diffusion weighted MRI (DW-MRI) is a noninvasive imaging technique that is used to detect changes in the apparent diffusion coefficient (ADC). The ADC value is an indicator of the movement of water within a tissue giving an average value of the flow and the distance the water molecule has moved. The decreased ADC in breast cancer reflects the underlying pattern of densely packed tumour cells, which inhibit effective motion of water molecules and restricted their diffusion

Dynamic, contrast-enhanced breast MRI (DCE-MRI) has been shown to be more accurate than mammography, ultrasound and clinical breast exam for the identification of tumour extent in the breast. However, DCE breast MRI is not currently utilized for the guidance of breast conservation surgery, primarily due to the differences in breast positioning during the MR imaging compared to the positioning in the surgical theatre. Therefore a supine positioning of the patient during MR imaging is preferred, which should result in a better matching of the images of the preoperative MRI and the later positioning in the operating room.

Stereotactic radiosurgery for the treatment of brain metastases delivers a high dose of radiation with excellent local control, but increases the likelihood of radiation necrosis. CEST is a promising technique for distinguishing radiation necrosis from tumour progression in brain metastases, but its application has been limited to a single MRI system and CEST sequence. This study explores the use of scaling of the magnetization transfer ratio (MTR) by the white matter (WM) of each patient for comparison across vendors/sequences. It was found that the WM-scaled MTR showed improved correspondence across the MR systems, across two CEST sequences.

Brain metastases are increasingly being treated with stereotactic radiosurgery; however, 20-30% of treated tumors locally recure post treatment. Hyperpolarized [1-13C]pyruvate magnetic resonance imaging (HP 13C MRI) is an emerging metabolic imaging modality that measures key metabolic phenotypes indicative of aggressive tumor phenotypes. Here we show that the pre-treatment tumor 13C-lactate to 13C-bicarbonate ratio – a marker of glycolysis and (indirectly) oxidative phosphorylation – measured via HP [1-13C]pyruvate MRI is a robust predictor of local recurrence (AUCROC=0.95, p=0.0008; AUCPRC=0.92) and can inform treatment decisions should the model predict a non-response to SRS.

Motivation: The metabolic profile of normal appearing brain tissue in patients with brain metastases may be related to the course of disease. Goal(s): To test whether patients with brain metastases exhibit differential metabolism in normal appearing brain parenchyma compared to healthy control participants. Approach: Hyperpolarized [1-13C]-pyruvate and T1w MRI were used to compare the metabolism and volumes of normal appearing brain regions in patients and healthy control participants. Results: The lactate-to-bicarbonate (p=0.0004) and lactate-to-pyruvate (p=0.04) ratios were significantly increased in the normal appearing brain parenchyma of patients compared to controls. Impact: The metabolic profile of normal appearing brain parenchyma in patients with brain metastases exhibits significantly increased glycolytic metabolism compared to healthy control brains when imaged using hyperpolarized [1-13C]-pyruvate MRI and may be related to the course of disease.