Extracellular acidosis differentiates pancreatitis and pancreatic cancer in mouse models using acidoCEST MRI.

Differentiating pancreatitis from pancreatic cancer would improve diagnostic specificity, and prognosticating pancreatitis that progresses to pancreatic cancer would also improve diagnoses of pancreas pathology. The high glycolytic metabolism of pancreatic cancer can cause tumor acidosis, and different levels of pancreatitis may also have different levels of acidosis, so that extracellular acidosis may be a diagnostic biomarker for these pathologies. AcidoCEST MRI can noninvasively measure extracellular pH (pHe) in the pancreas and pancreatic tissue.

Measuring Kidney Perfusion, pH, and Renal Clearance Consecutively Using MRI and Multispectral Optoacoustic Tomography.

To establish multi-modal imaging for the assessment of kidney pH, perfusion, and clearance rate using magnetic resonance imaging (MRI) and multispectral optoacoustic tomography (MSOT) in healthy mice. Kidney pH and perfusion values were measured on a pixel-by-pixel basis using the MRI acidoCEST and FAIR-EPI methods. Kidney filtration rate was measured by analyzing the renal clearance rate of IRdye 800 using MSOT.

Imaging Lung Cancer by Using Chemical Exchange Saturation Transfer MRI With Retrospective Respiration Gating.

Performing chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) in lung tissue is difficult because of motion artifacts. We, therefore, developed a CEST MRI acquisition and analysis method that performs retrospective respiration gating. Our method used an acquisition scheme with a short 200-millisecond saturation pulse that can accommodate the timing of the breathing cycle, and with saturation applied at frequencies in 0.

A comparison of exogenous and endogenous CEST MRI methods for evaluating in vivo pH.

Purpose: Extracellular pH (pHe) is an important biomarker for cancer cell metabolism. Acido-chemical exchange saturation transfer (CEST) MRI uses the contrast agent iopamidol to create spatial maps of pHe. Measurements of amide proton transfer exchange rates (k ) from endogenous CEST MRI were compared to pHe measurements by exogenous acido-CEST MRI to determine whether endogenous k could be used as a proxy for pHe measurements.

Detection of Enzyme Activity and Inhibition during Studies in Solution, In Vitro and In Vivo with CatalyCEST MRI.

Purpose: The detection of enzyme activities and evaluation of enzyme inhibitors have been challenging with magnetic resonance imaging (MRI). To address this need, we have developed a diamagnetic, nonmetallic contrast agent and a protocol known as catalyCEST MRI that uses chemical exchange saturation transfer (CEST) to detect enzyme activity as well as enzyme inhibition.

Procedures: We synthesized a diamagnetic MRI contrast agent that has enzyme responsive and enzyme unresponsive CEST signals.

Clinical Translation of Tumor Acidosis Measurements with AcidoCEST MRI.

Purpose: We optimized acido-chemical exchange saturation transfer (acidoCEST) magnetic resonance imaging (MRI), a method that measures extracellular pH (pHe), and translated this method to the radiology clinic to evaluate tumor acidosis.

Procedures: A CEST-FISP MRI protocol was used to image a flank SKOV3 tumor model. Bloch fitting modified to include the direct estimation of pH was developed to generate parametric maps of tumor pHe in the SKOV3 tumor model, a patient with high-grade invasive ductal carcinoma, and a patient with metastatic ovarian cancer.

Multislice CEST MRI improves the spatial assessment of tumor pH.

Purpose: Multislice maps of extracellular pH (pHe) are needed to interrogate the heterogeneities of tumors and normal organs. To address this need, we have developed a multislice chemical exchange saturation transfer (CEST) MRI acquisition method with a CEST spectrum-fitting method that measures in vivo pHe over a range of 6.3 to 7.

QUESPOWR MRI: QUantification of Exchange as a function of Saturation Power On the Water Resonance.

QUantification of Exchange as a function of Saturation Power On the Water Resonance (QUESPOWR) MRI is a new method that can estimate chemical exchange rates. This method acquires a series of OPARACHEE MRI acquisitions with a range of RF powers for the WALTZ16(∗) pulse train, which are applied on the water resonance. A QUESPOWR plot can be generated from the power dependence of the % water signal, which is similar to a QUESP plot that is generated from CEST MRI acquisition methods with RF saturation applied off-resonance from water.

Noninvasive detection of enzyme activity in tumor models of human ovarian cancer using catalyCEST MRI.

Purpose: We proposed to detect the in vivo enzyme activity of γ-glutamyl transferase (GGT) within mouse models of human ovarian cancers using catalyCEST MRI with a diamagnetic CEST agent.

Methods: A CEST-FISP MRI protocol and a diamagnetic CEST agent were developed to detect GGT enzyme activity in biochemical solution. A quantitative Michaelis-Menten enzyme kinetics study was performed to confirm that catalyCEST MRI can measure enzyme activity.

Respiration gating and Bloch fitting improve pH measurements with acidoCEST MRI in an ovarian orthotopic tumor model.

We have developed a MRI method that can measure extracellular pH in tumor tissues, known as acidoCEST MRI. This method relies on the detection of Chemical Exchange Saturation Transfer (CEST) of iopamidol, an FDA-approved CT contrast agent that has two CEST signals. A log ratio of the two CEST signals is linearly correlated with pH, but independent of agent concentration, endogenous T relaxation time, and B inhomogeneity.

A biomarker-responsive T MRI contrast agent.

Purpose: This study investigated a fundamentally new type of responsive MRI contrast agent for molecular imaging that alters T exchange (T ) properties after interacting with a molecular biomarker.

Methods: The contrast agent Tm-DO3A-oAA was treated with nitric oxide (NO) and O . The R and R relaxation rates of the reactant and product were measured with respect to concentration, temperature, and pH.

Design and optimization of pulsed Chemical Exchange Saturation Transfer MRI using a multiobjective genetic algorithm.

Pulsed Chemical Exchange Saturation Transfer (CEST) MRI experimental parameters and RF saturation pulse shapes were optimized using a multiobjective genetic algorithm. The optimization was carried out for RF saturation duty cycles of 50% and 90%, and results were compared to continuous wave saturation and Gaussian waveform. In both simulation and phantom experiments, continuous wave saturation performed the best, followed by parameters and shapes optimized by the genetic algorithm and then followed by Gaussian waveform.

A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals.

CatalyCEST MRI can detect enzyme activity by monitoring the change in chemical exchange with water after a contrast agent is cleaved by an enzyme. Often these molecules use paramagnetic metals and are delivered with an additional non-responsive reference molecule. To improve this approach for molecular imaging, a single diamagnetic agent with enzyme-responsive and enzyme-unresponsive CEST signals was synthesized and characterized.

A comparison of iopromide and iopamidol, two acidoCEST MRI contrast media that measure tumor extracellular pH.

Acidosis within tumor and kidney tissues has previously been quantitatively measured using a molecular imaging technique known as acidoCEST MRI. The previous studies used iopromide and iopamidol, two iodinated contrast agents that are approved for clinical CT diagnoses and have been repurposed for acidoCEST MRI studies. We aimed to compare the performance of the two agents for measuring pH by optimizing image acquisition conditions, correlating pH with a ratio of CEST effects from an agent, and evaluating the effects of concentration, endogenous T1 relaxation time and temperature on the pH-CEST ratio correlation for each agent.

Evaluations of Tumor Acidosis Within In Vivo Tumor Models Using Parametric Maps Generated with Acido CEST MRI.

Purpose: We aimed to develop pixelwise maps of tumor acidosis to aid in evaluating extracellular tumor pH (pHe) in cancer biology.

Procedures: MCF-7 and MDA-MB-231 mouse models were imaged during a longitudinal study. AcidoCEST MRI and a series of image processing methods were used to produce parametric maps of tumor pHe, and tumor pHe was also measured with a pH microsensor.

Measuring extracellular pH in a lung fibrosis model with acidoCEST MRI.

Purpose: A feed-forward loop involving lactic acid production may potentially occur during the formation of idiopathic pulmonary fibrosis. To provide evidence for this feed-forward loop, we used acidoCEST MRI to measure the extracellular pH (pHe), while also measuring percent uptake of the contrast agent, lesion size, and the apparent diffusion coefficient (ADC).

Procedures: We developed a respiration-gated version of acidoCEST MRI to improve the measurement of pHe and percent uptake in lesions.

The reciprocal linear QUEST analysis method facilitates the measurements of chemical exchange rates with CEST MRI.

Magnetic resonance imaging (MRI) contrast media that are detected via chemical exchange saturation transfer (CEST) often require an accurate estimation of their chemical exchange rate, kex . A variety of analysis methods have been proposed to estimate kex , including the nonlinear QUEST analysis method that evaluates the CEST amplitude as a function of saturation time. We have derived a linear version of QUEST, termed the Reciprocal Linear QUEST (RL-QUEST) method.

The Hanes-Woolf linear QUESP method improves the measurements of fast chemical exchange rates with CEST MRI.

Purpose: Contrast agents for chemical exchange saturation transfer MRI often require an accurate measurement of the chemical exchange rate. Many analysis methods have been reported that measure chemical exchange rates. Additional analysis methods were derived as part of this study.

A catalyCEST MRI contrast agent that detects the enzyme-catalyzed creation of a covalent bond.

CatalyCEST MRI can detect enzyme activity by employing contrast agents that are detected through chemical exchange saturation transfer (CEST). A CEST agent, Tm-DO3A-cadaverine, has been designed to detect the catalytic activity of transglutaminase (TGase), which creates a covalent bond between the agent and the side chain of a glutamine amino acid residue. CEST appeared at -9.