Frequency-specific SSFP for hyperpolarized C metabolic imaging at 14.1 T

Metabolic imaging of hyperpolarized [1-¹³C] pyruvate co-polarized with [¹³C]urea by dynamic nuclear polarization with rapid dissolution is a promising new method for assessing tumor metabolism and perfusion simultaneously in vivo. Novel pulse sequences are required to enable dynamic imaging of multiple ¹³C spectral lines with high spatiotemporal resolution. The goal of this study was to investigate a new frequency-specific approach for rapid metabolic imaging of multiple ¹³C resonances using the spectral selectivity of steady-state free precession pulse (SSFP) trains. Methods developed in simulations were implemented in a dynamic frequency-cycled balanced SSFP pulse sequence on a 14.1-T animal magnetic resonance imaging scanner. This acquisition was tested in thermal and hyperpolarized phantom imaging studies and in a transgenic mouse with prostate cancer.     

In vivo measurement of normal rat intracellular pyruvate and lactate levels after injection of hyperpolarized [1-(13)C]alanine

Hyperpolarized technology utilizing dynamic nuclear polarization has enabled rapid and high-sensitivity measurements of ¹³C metabolism in vivo. The most commonly used in vivo agent for hyperpolarized ¹³C metabolic imaging thus far has been [1-¹³C]pyruvate. In preclinical studies, not only is its uptake detected, but also its intracellular enzymatic conversion to metabolic products including [1-¹³C]lactate and [1-¹³C]alanine. However, the ratio of ¹³C-lactate/¹³C-pyruvate measured in this data does not accurately reflect cellular values since much of the [1-¹³C]pyruvate is extracellular depending on timing, vascular properties, and extracellular space and monocarboxylate transporter activity. In order to measure the relative levels of intracellular pyruvate and lactate, in this project we hyperpolarized [1-¹³C]alanine and monitored the in vivo conversion to [1-¹³C]pyruvate and then the subsequent conversion to [1-¹³C]lactate. The intracellular lactate-to-pyruvate ratio of normal rat tissue measured with hyperpolarized [1-¹³C]alanine was 4.89±0.61 (mean±S.E.) as opposed to a ratio of 0.41±0.03 when hyperpolarized [1-¹³C]pyruvate was injected.     

In vivo C magnetic resonance spectroscopy of a human brain tumor after application of C-1-enriched glucose

Objectives

As a unique tool to assess metabolic fluxes noninvasively, ¹³C magnetic resonance spectroscopy (MRS) could help to characterize and understand malignancy in human tumors. However, its low sensitivity has hampered applications in patients. The aim of this study was to demonstrate that with sensitivity-optimized localized ¹³C MRS and intravenous infusion of [1-¹³C]glucose under euglycemia, it is possible to assess the dynamic conversion of glucose into its metabolic products in vivo in human glioma tissue.

Materials and Methods

Measurements were done at 3 T with a broadband single RF channel and a quadrature ¹³C surface coil inserted in a ¹H volume coil. A ¹H/¹³C polarization transfer sequence was applied, modified for localized acquisition, alternatively in two (50 ml) voxels, one encompassing the tumor and the other normal brain tissue.

Results

After about 20 min of [1-¹³C]glucose infusion, a [3-¹³C]lactate signal appeared among several resonances of metabolic products of glucose in MR spectra of the tumor voxel. The resonance of [3-¹³C]lactate was absent in MR spectra from contralateral tissue. In addition, the intensity of [1-¹³C]glucose signals in the tumor area was about 50% higher than that in normal tissue, likely reflecting more glucose in extracellular space due to a defective blood–brain barrier. The signal intensity for metabolites produced in or via the tricarboxylic acid (TCA) cycle was lower in the tumor than in the contralateral area, albeit that the ratios of isotopomer signals were comparable.

Conclusion

With an improved ¹³C MRS approach, the uptake of glucose and its conversion into metabolites such as lactate can be monitored noninvasively in vivo in human brain tumors. This opens the way to assessing metabolic activity in human tumor tissue.     

The feasibility of assessing branched-chain amino acid metabolism in cellular models of prostate cancer with hyperpolarized [1-C]-ketoisocaproate

Recent advancements in the field of hyperpolarized ¹³C magnetic resonance spectroscopy (MRS) have yielded powerful techniques capable of real-time analysis of metabolic pathways. These non-invasive methods have increasingly shown application in impacting disease diagnosis and have further been employed in mechanistic studies of disease onset and progression. Our goals were to investigate branched-chain aminotransferase (BCAT) activity in prostate cancer with a novel molecular probe, hyperpolarized [1-¹³C]-2-ketoisocaproate ([1-¹³C]-KIC), and explore the potential of branched-chain amino acid (BCAA) metabolism to serve as a biomarker. Using traditional spectrophotometric assays, BCAT enzymatic activities were determined in vitro for various sources of prostate cancer (human, transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse and human cell lines). These preliminary studies indicated that low levels of BCAT activity were present in all models of prostate cancer but enzymatic levels are altered significantly in prostate cancer relative to healthy tissue. The MR spectroscopic studies were conducted with two cellular models (PC-3 and DU-145) that exhibited levels of BCAA metabolism comparable to the human disease state. Hyperpolarized [1-¹³C]-KIC was administered to prostate cancer cell lines, and the conversion of [1-¹³C]-KIC to the metabolic product, [1-¹³C]-leucine ([1-¹³C]-Leu), could be monitored via hyperpolarized ¹³C MRS.     

Multi-band frequency encoding method for metabolic imaging with hyperpolarized [1-(13)C]pyruvate

A new method was developed for simultaneous spatial localization and spectral separation of multiple compounds based on a single echo, by designing the acquisition to place individual compounds in separate frequency encoding bands. This method was specially designed for rapid and robust metabolic imaging of hyperpolarized (13)C substrates and their metabolic products, and was investigated in phantom studies and studies in normal mice and transgenic models of prostate cancer to provide rapid metabolic imaging of hyperpolarized [1-(13)C]pyruvate and its metabolic products [1-(13)C]lactate and [1-(13)C]alanine at spatial resolutions up to 3mm in-plane. Elevated pyruvate and lactate signals in the vicinity of prostatic tissues were observed in transgenic tumor mice. The multi-band frequency encoding technique enabled rapid metabolic imaging of hyperpolarized (13)C compounds with important advantages over prior approaches, including less complicated acquisition and reconstruction methods.     

Design of spectral-spatial outer volume suppression RF pulses for tissue specific metabolic characterization with hyperpolarized C pyruvate

[1-¹³C] pyruvate pre-polarized via DNP has been used in animal models to probe changes in metabolic enzyme activities in vivo. To more accurately assess the metabolic state and its change from disease progression or therapy in a specific region or tissue in vivo, it may be desirable to separate the downstream ¹³C metabolite signals resulting from the metabolic activity within the tissue of interest and those brought into the tissue by perfusion. In this study, a spectral-spatial saturation pulse that selectively saturates the signal from the metabolic products [1-¹³C] lactate and [1-¹³C] alanine was designed and implemented as outer volume suppression for localized MRSI acquisition. Preliminary in vivo results showed that the suppression pulse did not prevent the pre-polarized pyruvate from being delivered throughout the animal while it saturated the metabolites within the targeted saturation region.     

Cancer recurrence monitoring using hyperpolarized [1-13C]pyruvate metabolic imaging in murine breast cancer model

The purpose of this work was to study the anatomic and metabolic changes that occur with tumor progression, regression and recurrence in a switchable MYC-driven murine breast cancer model. Serial ¹H MRI and hyperpolarized [1-¹³C]pyruvate metabolic imaging were used to investigate the changes in tumor volume and glycolytic metabolism over time during the multistage tumorigenesis. We show that acute de-induction of MYC expression in established tumors results in rapid tumor regression and significantly reduced glycolytic metabolism as measured by pyruvate-to-lactate conversion. Moreover, cancer recurrences occurring at the tumor sites independently of MYC expression were observed to accompany markedly increased lactate production.     

Analysis of hyperpolarized dynamic C lactate imaging in a transgenic mouse model of prostate cancer

This study investigated the application of an acquisition that selectively excites the [1-¹³C]lactate resonance and allows dynamic tracking of the conversion of ¹³C-lactate from hyperpolarized ¹³C-pyruvate at a high spatial resolution. In order to characterize metabolic processes occurring in a mouse model of prostate cancer, 20 sequential 3D images of ¹³C-lactate were acquired 5 s apart using a pulse sequence that incorporated a spectral–spatial excitation pulse and a flyback echo-planar readout to track the time course of newly converted ¹³C-lactate after injection of prepolarized ¹³C-pyruvate. The maximum lactate signal (MLS), full-width half-maximum (FWHM), time to the peak ¹³C-lactate signal (TTP) and area under the dynamic curve were calculated from the dynamic images of 10 TRAMP mice and two wild-type controls. The regional variation in ¹³C-lactate associated with the injected pyruvate was demonstrated by the peak of the ¹³C-lactate signal occurring earlier in the kidney than in the tumor region. The intensity of the dynamic ¹³C-lactate curves also varied spatially within the tumor, illustrating the heterogeneity in metabolism that was most prominent in more advanced stages of disease development. The MLS was significantly higher in TRAMP mice that had advanced disease.     

Development of high resolution 3D hyperpolarized carbon-13 MR molecular imaging techniques

The goal of this project was to develop and apply techniques for T₂ mapping and 3D high resolution (1.5 mm isotropic; 0.003 cm³) ¹³C imaging of hyperpolarized (HP) probes [1-¹³C]lactate, [1-¹³C]pyruvate, [2-¹³C]pyruvate, and [¹³C,¹⁵N₂]urea in vivo. A specialized 2D bSSFP sequence was implemented on a clinical 3T scanner and used to obtain the first high resolution T₂ maps of these different hyperpolarized compounds in both rats and tumor-bearing mice. These maps were first used to optimize timings for highest SNR for single time-point 3D bSSFP acquisitions with a 1.5 mm isotropic spatial resolution of normal rats. This 3D acquisition approach was extended to serial dynamic imaging with 2-fold compressed sensing acceleration without changing spatial resolution. The T₂ mapping experiments yielded measurements of T₂ values of > 1 s for all compounds within rat kidneys/vasculature and TRAMP tumors, except for [2-¹³C]pyruvate which was ~ 730 ms and ~ 320 ms, respectively. The high resolution 3D imaging enabled visualization the biodistribution of [1-¹³C]lactate, [1-¹³C]pyruvate, and [2-¹³C]pyruvate within different kidney compartments as well as in the vasculature. While the mouse anatomy is smaller, the resolution was also sufficient to image the distribution of all compounds within kidney, vasculature, and tumor. The development of the specialized 3D sequence with compressed sensing provided improved structural and functional assessments at a high (0.003 cm³) spatial and 2 s temporal resolution in vivo utilizing HP ¹³C substrates by exploiting their long T₂ values. This 1.5 mm isotropic resolution is comparable to ¹H imaging and application of this approach could be extended to future studies of uptake, metabolism, and perfusion in cancer and other disease models and may ultimately be of value for clinical imaging.     

Fast volumetric spatial-spectral MR imaging of hyperpolarized C-labeled compounds using multiple echo 3D bSSFP

Purpose

The goal of this work was to develop a fast 3D chemical shift imaging technique for the noninvasive measurement of hyperpolarized ¹³C-labeled substrates and metabolic products at low concentration.

Materials and Methods

Multiple echo 3D balanced steady state magnetic resonance imaging (ME-3DbSSFP) was performed in vitro on a syringe containing hyperpolarized [1,3,3-2H3; 1-¹³C]2-hydroxyethylpropionate (HEP) adjacent to a ¹³C-enriched acetate phantom, and in vivo on a rat before and after intravenous injection of hyperpolarized HEP at 1.5 T. Chemical shift images of the hyperpolarized HEP were derived from the multiple echo data by Fourier transformation along the echoes on a voxel by voxel basis for each slice of the 3D data set.

Results

ME-3DbSSFP imaging was able to provide chemical shift images of hyperpolarized HEP in vitro, and in a rat with isotropic 7-mm spatial resolution, 93 Hz spectral resolution and 16-s temporal resolution for a period greater than 45 s.

Conclusion

Multiple echo 3D bSSFP imaging can provide chemical shift images of hyperpolarized ¹³C-labeled compounds in vivo with relatively high spatial resolution and moderate spectral resolution. The increased signal-to-noise ratio of this 3D technique will enable the detection of hyperpolarized ¹³C-labeled metabolites at lower concentrations as compared to a 2D technique.     

Measuring the link between cardiac mechanical function and metabolism during hyperpolarized 13C-pyruvate magnetic resonance experiments

PurposeThe goal of this study was to develop a methodology to investigate the relationship between contractile function and hyperpolarized (HP) [1-¹³C]pyruvate metabolism in a small animal model. To achieve sufficient signal from HP ¹³C compounds, HP ¹³C MRS/MRSI has required relatively large infusion volumes relative to the total blood volume in small animal models, which may affect cardiac function.MethodsEight female Sprague Dawley rats were imaged on a 4.7T scanner with a dual tuned ¹H/¹³C volume coil. ECG and respiratory gated k-t spiral MRSI and an IDEAL based reconstruction to determine [1-¹³C]pyruvate metabolism in the myocardium. This was coupled with ¹H cine MRI to determine ventricular volumes and mechanical function pre- and post-infusion of [1-¹³C]pyruvate. For comparison to the [1-¹³C]pyruvate experiments, three female Sprague Dawley rats were imaged with ¹H cine MRI to determine myocardial function pre- and post-saline infusion.ResultsWe demonstrated significant changes in cardiac contractile function between pre- and post-infusion of [1-¹³C]pyruvate. Specifically, there was an increase in end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF). Additionally, the ventricular vascular coupling ratio (VVCR) showed an improvement after [1-¹³C]pyruvate infusion, indicating increased systolic performance due to an increased arterial load. There was a moderate to strong relationship between the downstream metabolic conversion of pyruvate to bicarbonate and a strong relationship between the conversion of pyruvate to lactate and the cardiac mechanical function response.ConclusionThe infusion of [1-¹³C]pyruvate resulted in demonstrable increases in contractile function which was related to pyruvate conversion to bicarbonate and lactate. The combined effects of the infusion volume and inotropic effects of pyruvate metabolism likely explains the augmentation in myocardial mechanical function seen in these experiments. Given the relationship between pyruvate metabolism and contractile function observed in this study, this methodological approach may be utilized to better understand cardiac metabolic and functional remodeling in heart disease.     

Rapid sequential injections of hyperpolarized [1-C]pyruvate in vivo using a sub-kelvin,multi-sample DNP polarizer

The development of hyperpolarized technology utilizing dynamic nuclear polarization (DNP) has enabled the rapid measurement of ¹³C metabolism in vivo with very high SNR. However, with traditional DNP equipment, consecutive injections of a hyperpolarized compound in an animal have been subject to a practical minimum time between injections governed by the polarization build-up time, which is on the order of an hour for [1-¹³C]pyruvate. This has precluded the monitoring of metabolic changes occurring on a faster time scale. In this study, we demonstrated the ability to acquire in vivo dynamic magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic imaging (MRSI) data in normal rats with a 5 min interval between injections of hyperpolarized [1-¹³C]pyruvate using a prototype, sub-Kelvin dynamic nuclear polarizer with the capability to simultaneously polarize up to 4 samples and dissolve them in rapid succession. There were minimal perturbations in the hyperpolarized spectra as a result of the multiple injections, suggesting that such an approach would not confound the investigation of metabolism occurring on this time scale. As an initial demonstration of the application of this technology and approach for monitoring rapid changes in metabolism as a result of a physiological intervention, we investigated the pharmacodynamics of the anti-cancer agent dichloroacetate (DCA), collecting hyperpolarized data before administration of DCA, 1 min after administration, and 6 min after administration. Dramatic increases in ¹³C-bicarbonate were detected just 1 min (as well as 6 min) after DCA administration.     

Use of hyperpolarized [1-C]pyruvate and [2-C]pyruvate to probe the effects of the anticancer agent dichloroacetate on mitochondrial metabolism in vivo in the normal rat

Development of hyperpolarized technology utilizing dynamic nuclear polarization has enabled the measurement of ¹³C metabolism in vivo at very high signal-to-noise ratio (SNR). In vivo mitochondrial metabolism can, in principle, be monitored with pyruvate, which is catalyzed to acetyl-CoA via pyruvate dehydrogenase (PDH). The purpose of this work was to determine whether the compound sodium dichloroacetate (DCA) could aid the study of mitochondrial metabolism with hyperpolarized pyruvate. DCA stimulates PDH by inhibiting its inhibitor, pyruvate dehydrogenase kinase. In this work, hyperpolarized [1-¹³C]pyruvate and [2-¹³C]pyruvate were used to probe mitochondrial metabolism in normal rats. Increased conversion to bicarbonate (+ 181±69%, P=.025) was measured when [1-¹³C]pyruvate was injected after DCA administration, and increased glutamate (+ 74±23%, P=.004), acetoacetate (+ 504±281%, P=.009) and acetylcarnitine (+ 377±157%, P=.003) were detected when [2-¹³C]pyruvate was used.     

Hyperpolarized 13C MRS Cardiac Metabolism Studies in Pigs: Comparison Between Surface and Volume Radiofrequency Coils

Cardiac metabolism assessment with hyperpolarized ¹³C magnetic resonance spectroscopy in pig models requires the design of dedicated coils capable of providing large field of view with high signal-to-noise ratio (SNR) data. This work presents a comparison between a commercial ¹³C quadrature birdcage coil and a homebuilt ¹³C circular coil both designed for hyperpolarized studies of pig heart with a clinical 3T scanner. In particular, the simulation of the two coils is described by developing an SNR model for coil performance prediction and comparison. While coil resistances were calculated from Ohm’s law, the magnetic field patterns and sample-induced resistances were calculated using a numerical finite-difference time-domain algorithm. After the numerical simulation of both coils, the results are presented as SNR-versus-depth profiles using experimental SNR extracted from the [1-¹³C]acetate phantom chemical shift image and with a comparison of metabolic maps acquired by hyperpolarized [1-¹³C]pyruvate injected in a pig. The accuracy of the developed SNR models was demonstrated by good agreement between the theoretical and experimental coil SNR-versus-depth profiles.     

Detection of intracellular lactate with localized diffusion {1H-13C}-spectroscopy in rat glioma in vivo

The aim of this study was to compare the diffusion characteristic of lactate and alanine in a brain tumor model to that of normal brain metabolites known to be mainly intracellular such as N-acetylaspartate or creatine. The diffusion of (13)C-labeled metabolites was measured in vivo with localized NMR spectroscopy at 9.4 T (400 MHz) using a previously described localization and editing pulse sequence known as ACED-STEAM ('adiabatic carbon editing and decoupling'). (13)C-labeled glucose was administered and the apparent diffusion coefficients of the glycolytic products, {(1)H-(13)C}-lactate and {(1)H-(13)C}-alanine, were determined in rat intracerebral 9L glioma. To obtain insights into {(1)H-(13)C}-lactate compartmentation (intra- versus extracellular), the pulse sequence used very large diffusion weighting (50 ms/microm(2)). Multi-exponential diffusion attenuation of the lactate metabolite signals was observed. The persistence of a lactate signal at very large diffusion weighting provided direct experimental evidence of significant intracellular lactate concentration. To investigate the spatial distribution of lactate and other metabolites, (1)H spectroscopic images were also acquired. Lactate and choline-containing compounds were consistently elevated in tumor tissue, but not in necrotic regions and surrounding normal-appearing brain. Overall, these findings suggest that lactate is mainly associated with tumor tissue and that within the time-frame of these experiments at least some of the glycolytic product ([(13)C] lactate) originates from an intracellular compartment.     

Compressed sensing for resolution enhancement of hyperpolarized 13C flyback 3D-MRSI

High polarization of nuclear spins in liquid state through dynamic nuclear polarization has enabled the direct monitoring of 13C metabolites in vivo at very high signal-to-noise, allowing for rapid assessment of tissue metabolism. The abundant SNR afforded by this hyperpolarization technique makes high-resolution 13C 3D-MRSI feasible. However, the number of phase encodes that can be fit into the short acquisition time for hyperpolarized imaging limits spatial coverage and resolution. To take advantage of the high SNR available from hyperpolarization, we have applied compressed sensing to achieve a factor of 2 enhancement in spatial resolution without increasing acquisition time or decreasing coverage. In this paper, the design and testing of compressed sensing suited for a flyback 13C 3D-MRSI sequence are presented. The key to this design was the undersampling of spectral k-space using a novel blipped scheme, thus taking advantage of the considerable sparsity in typical hyperpolarized 13C spectra. Phantom tests validated the accuracy of the compressed sensing approach and initial mouse experiments demonstrated in vivo feasibility.     

Transmit-Only/Receive-Only Radiofrequency System for Hyperpolarized 13C MRS Cardiac Metabolism Studies in Pigs

Hyperpolarized ¹³C magnetic resonance spectroscopy in pig models enables metabolic activity mapping, providing a powerful tool for the study of the heart physiology, but requires the development of dedicated radiofrequency coils, capable of providing large field of view with high signal-to-noise ratio (SNR) data. This work describes the simulations and the tests of a transmit-only (TX) volume coil/receive-only (RX) surface coil both designed for hyperpolarized studies of pig heart with a clinical 3T scanner. The coil characterization is performed by developing an SNR model for coil performance in terms of coil resistance, sample-induced resistance and magnetic field pattern. In particular, coil resistances were calculated from Ohm’s law, while magnetic field patterns and sample-induced resistances were calculated using a numerical finite-difference time-domain algorithm. Experimental phantom chemical shift image, showed good agreement with the theoretical SNR-vs-depth profiles and highlighted the advantage of the novel configuration over the single transmit–receive coils throughout the volume of interest for cardiac imaging in pig. Finally, the TX-birdcage/RX-circular configuration was tested by acquiring metabolic maps with hyperpolarized [1-13C] pyruvate injected i.v. in a pig. The results of the phantom and pig experiments show the ability of the coil configuration to image well the metabolites distribution.     

13C/12C-Untersuchungen an Tumorzellen

Abstract

The metabolism of tumor-cells differs in many ways from normal (healthy) cells. One of the major differences is the high glycolytic activity in tumor-cells with the subsequent formation of lactate from glucose, even in the presence of oxygen. The question whether this high rate of glycolysis has any effect on the ¹³C/¹²C-relation of the cells is examined in experiments with a tumor-cell line (HT29) and in specimens of human breast cancer.

The HT29 cells show a clear decrease in ¹³C content compared to their culture medium (Δδ = 3.28‰).

Tissue from human breast cancer has more ¹³C than normal breast tissue taken from the same patient ((Δδ = 2.74‰). But the content of fat is much higher in the normal tissue and its δ-value is negatively correlated with its fat content. It is concluded that the difference between normal and tumor tissue is due to the heterogeneous composition of the normal tissue samples.     

Pulse sequence for dynamic volumetric imaging of hyperpolarized metabolic products

Dynamic nuclear polarization and dissolution of a ¹³C-labeled substrate enables the dynamic imaging of cellular metabolism. Spectroscopic information is typically acquired, making the acquisition of dynamic volumetric data a challenge. To enable rapid volumetric imaging, a spectral-spatial excitation pulse was designed to excite a single line of the carbon spectrum. With only a single resonance present in the signal, an echo-planar readout trajectory could be used to resolve spatial information, giving full volume coverage of 32 × 32 × 16 voxels every 3.5 s. This high frame rate was used to measure the different lactate dynamics in different tissues in a normal rat model and a mouse model of prostate cancer.     

Investigation of prostate cancer using diffusion-weighted intravoxel incoherent motion imaging

Purpose

The objective of this work was to evaluate the diagnostic performance of the intravoxel incoherent motion (IVIM) model to differentiate between healthy and malignant prostate tissue.

Materials and Methods

Regions of interest were drawn in healthy and cancerous tissue of 13 patients with histologically proven prostate carcinoma and fitted to a monoexponential model [yielding the apparent diffusion coefficient (ADC)] and the IVIM signal equation (yielding the perfusion fraction f, the diffusion constant D and the pseudodiffusion coefficient of perfusion D?). Parameter maps were calculated for all parameters.

Results

The ADC, D and f were significantly (P<.005) lowered in cancerous tissue (1.01±0.22 μm²/ms, 0.84±0.19 μm²/ms and 14.27±7.10%, respectively) compared to benign tissue (1.49±0.17 μm²/ms, 1.21±0.22 μm²/ms and 21.25±8.32%, respectively). Parameter maps of D and f allowed for a delineation of the tumor, but showed higher variations compared to the ADC map.

Conclusion

Apparent diffusion coefficient maps provide better diagnostic performance than IVIM maps for tumor detection. However, the results suggest that the reduction of the ADC in prostate cancer stems not only from changes in cellularity but also from perfusion effects. IVIM imaging might hold promise for the diagnosis of other prostatic lesions.