Hyperpolarized Imaging

Hyperpolarizing Concentrated Metronidazole 15NO2 Group Over Six Chemical Bonds with More Than 15% Polarization and 20 Minute Lifetime

Hyperpolarization of 15N-labeled antibiotic metronidazole-15N3 is demonstrated using SABRE-SHEATH technique. A 15NO2 group is hyperpolarized via spin relays created by three  15N spins in metronidazole-15N3. In less than a minute of parahydrogen bubbling at ~0.4 μT, a high level of nuclear spin polarization P15N of ~16% is achieved on all three 15N sites at up to ~41 mM concentration. This product of 15N polarization and concentration of 15N spins is ~6-fold better than any previous value for 15N SABRE-derived hyperpolarization. At 1.4 T, T1 of the 15NO2 group is ~10 min. The large polarization and long T1 offer great potential for a wide range of in vivo metabolic applications from hypoxia sensing to theranostic imaging.

Dynamic metabolic imaging of hyperpolarized [2-13C]pyruvate using spiral CSI with alternating spectral band excitation

Hyperpolarized [2-13C] pyruvate permits the ability to follow the 13C label beyond flux through pyruvate dehydrogenase complex and investigate the incorporation of acetyl-CoA into different metabolic pathways. However, chemical shift imaging (CSI) with [2-13C] pyruvate is challenging due to the large spectral dispersion of the resonances. In this work, we presented a method that allows CSI of widely separated resonances without chemical shift displacement artifact, acquiring multiple frequency bands alternately to obtain dynamic time-course information. This approach enables robust imaging of downstream metabolic products of acetyl-CoA with hyperpolarized [2-13C] pyruvate.

Metabolic response of glioma to dichloroacetate measured in vivo by hyperpolarized (13)C magnetic resonance spectroscopic imaging​

The metabolic phenotype that derives disproportionate energy via glycolysis in solid tumors, including glioma, leads to elevated lactate labeling in metabolic imaging using hyperpolarized [1-13C]pyruvate. Although the pyruvate dehydrogenase (PDH)–mediated flux from pyruvate to acetyl coenzyme A can be indirectly measured through the detection of carbon-13 (13C)-labeled bicarbonate, it has proven difficult to visualize 13C-bicarbonate at high enough levels from injected [1-13C]pyruvate for quantitative analysis in brain. The aim of this study is to improve the detection of 13C-labeled metabolites, in particular bicarbonate, in glioma and normal brain in vivo and to measure the metabolic response to dichloroacetate, which upregulates PDH activity.

Measuring mitochondrial metabolism in rat brain in vivo using MR Spectroscopy of hyperpolarized [2-¹³C]pyruvate

Hyperpolarized [1-(13) C]pyruvate ([1-(13) C]Pyr) has been used to assess metabolism in healthy and diseased states, focusing on the downstream labeling of lactate (Lac), bicarbonate and alanine. Although hyperpolarized [2-(13) C]Pyr, which retains the labeled carbon when Pyr is converted to acetyl-coenzyme A, has been used successfully to assess mitochondrial metabolism in the heart, the application of [2-(13) C]Pyr in the study of brain metabolism has been limited to date, with Lac being the only downstream metabolic product reported previously. In this study, single-time-point chemical shift imaging data were acquired from rat brain in vivo. [5-(13) C]Glutamate, [1-(13) C]acetylcarnitine and [1-(13) C]citrate were detected in addition to resonances from [2-(13) C]Pyr and [2-(13) C]Lac. Brain metabolism was further investigated by infusing dichloroacetate, which upregulates Pyr flux to acetyl-coenzyme A. After dichloroacetate administration, a 40% increase in [5-(13) C]glutamate from 0.014 ± 0.004 to 0.020 ± 0.006 (p = 0.02), primarily from brain, and a trend to higher citrate (0.002 ± 0.001 to 0.004 ± 0.002) were detected, whereas [1-(13) C]acetylcarnitine was increased in peripheral tissues. This study demonstrates, for the first time, that hyperpolarized [2-(13) C]Pyr can be used for the in vivo investigation of mitochondrial function and tricarboxylic acid cycle metabolism in brain.

Hyperpolarized 13C metabolic imaging using dissolution dynamic nuclear polarization

This article describes the basic physics of dissolution dynamic nuclear polarization (dissolution‐DNP), and the impact of the resulting highly nonequilibrium spin states, on the physics of magnetic resonance imaging (MRI) detection. The hardware requirements for clinical translation of this technology are also presented. For studies that allow the use of externally administered agents, hyperpolarization offers a way to overcome normal magnetic resonance sensitivity limitations, at least for a brief T1‐dependent observation window. A 10,000–100,000‐fold signal‐to‐noise advantage provides an avenue for real‐time measurement of perfusion, metabolite transport, exchange, and metabolism. The principles behind these measurements, as well as the choice of agent, and progress toward the application of hyperpolarized 13C metabolic imaging in oncology, cardiology, and neurology are reviewed.

Multi-Channel Metabolic Imaging, with SENSE reconstruction, of Hyperpolarized [1-13C] Pyruvate in a Live Rat at 3.0 tesla on a Clinical MR Scanner

We report metabolic images of 13C, following injection of a bolus of of hyperpolarized [1-13C] pyruvate in a live rat. The data were acquired on a clinical scanner, using custom coils for volume transmission and array reception. Proton blocking of all carbon resonators enabled proton anatomic imaging with the system body coil, to allow for registration of anatomic and metabolic images, for which good correlation was achieved, with some anatomic features (kidney and heart) clearly visible in a carbon image, without reference to the corresponding proton image. Parallel imaging with sensitivity encoding was used to increase the spatial resolution in the SI direction of the rat. The signal to noise ratio in was in some instances unexpectedly high in the parallel images; variability of the polarization among different trials, plus partial volume effects, are noted as a possible cause of this

Kinetic modeling of hyperpolarized 13C1-pyruvate metabolism in normal rats and TRAMP mice

The purpose of the study was to investigate metabolic exchange between 13C1-pyruvate, 13C1-lactate, and 13C1-alanine in preclinical model systems using kinetic modeling of dynamic hyperpolarized 13C spectroscopic data and to examine the relationship between fitted parameters and dose–response.

T2 relaxation times of 13C metabolites in a rat hepatocellular carcinoma model measured in vivo using 13C‐MRS of hyperpolarized [1‐13C]pyruvate

NMR hyperpolarization of uniformly 15N-labeled metronidazole-15N3 is demonstrated using SABRE-SHEATH (Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). In this antibiotic, a 15NO2 group is hyperpolarized via spin relays created by 15N spins in metronidazole-15N3, and the polarization is transferred from parahydrogen-derived hydrides over six chemical bonds. This efficient spin-relayed mechanism of polarization transfer is supported by measurements of polarization dynamics and T1 relaxation in micro-Tesla magnetic fields. In less than a minute of parahydrogen bubbling at ~0.4 μT, a high level of nuclear spin polarization P15N of ~16% is achieved on all three 15N sites of metronidazole-15N3 at up to ~41 mM concentration. This product of 15N polarization and concentration of 15N spins is ~6-fold better than any previous value for 15N SABRE-derived hyperpolarization. At 1.4 T, the hyperpolarized state of the 15NO2 group of this antibiotic persists for tens of minutes (T1~10 min), in part because its 15N spin has no detectable spin-spin couplings with protons of the molecule. A novel synthesis achieving robust uniform 15N enrichment of metronidazole is reported with 15% yield over three steps. This synthetic approach should be suitable for preparation of other 15N-labeled nitroimidazole derivatives, potentially enabling a wide range of in vivo metabolic probes from hypoxia sensing to theranostic imaging.

Metabolic imaging in the anesthetized rat brain using hyperpolarized [1‐13C] pyruvate and [1‐13C] ethyl pyruvate

Formulation, polarization, and dissolution conditions were developed to obtain a stable hyperpolarized solution of [1‐13C]‐ethyl pyruvate. A maximum tolerated concentration and injection rate were determined, and 13C spectroscopic imaging was used to compare the uptake of hyperpolarized [1‐13C]‐ethyl pyruvate relative to hyperpolarized [1‐13C]‐pyruvate into anesthetized rat brain. Hyperpolarized [1‐13C]‐ethyl pyruvate and [1‐13C]‐pyruvate metabolic imaging in normal brain is demonstrated and quantified in this feasibility and range‐finding study.

Application of subsecond spiral chemical shift imaging to real‐time multislice metabolic imaging of the rat in vivo after injection of hyperpolarized 13C1‐pyruvate

Dynamic nuclear polarization can create hyperpolarized compounds with MR signal‐to‐noise ratio enhancements on the order of 10,000‐fold. Both exogenous and normally occurring endogenous compounds can be polarized, and their initial concentration and downstream metabolic products can be assessed using MR spectroscopy. Given the transient nature of the hyperpolarized signal enhancement, fast imaging techniques are a critical requirement for real‐time metabolic imaging. We report on the development of an ultrafast, multislice, spiral chemical shift imaging sequence, with subsecond acquisition time, achieved on a clinical MR scanner. The technique was used for dynamic metabolic imaging in rats, with measurement of time‐resolved spatial distributions of hyperpolarized 13C1‐pyruvate and metabolic products 13C1‐lactate and 13C1‐alanine, with a temporal resolution of as fast as 1 s. Metabolic imaging revealed different signal time courses in liver from kidney. These results demonstrate the feasibility of real‐time, hyperpolarized metabolic imaging and highlight its potential in assessing organ‐specific kinetic parameters.

In Vivo Carbon-13 Dynamic MRS and MRSI of Normal and Fasted Rat Liver with Hyperpolarized 13C-Pyruvate

The use of in vivo 13C nuclear magnetic resonance spectroscopy in probing metabolic pathways to study normal metabolism and characterize disease physiology has been limited by its low sensitivity. However, recent technological advances have enabled greater than 50,000-fold enhancement of liquid-state polarization of metabolically active 13C substrates, allowing for rapid assessment of 13C metabolism in vivo. The present study applied hyperpolarized 13C magnetic resonance spectroscopy to the investigation of liver metabolism, demonstrating for the first time the feasibility of applying this technology to detect differences in liver metabolic states. [1-13C]pyruvate was hyperpolarized with a dynamic nuclear polarization instrument and injected into normal and fasted rats. The uptake of pyruvate and its conversion to the metabolic products lactate and alanine were observed with slice-localized dynamic magnetic resonance spectroscopy and 3D magnetic resonance spectroscopic imaging (3D-MRSI). Significant differences in lactate to alanine ratio (P < 0.01) between normal and fasted rat liver slice dynamic spectra were observed. 3D-MRSI localized to the fasted livers demonstrated significantly decreased 13C-alanine levels (P < 0.01) compared to normal. This study presents the initial demonstration of characterizing metabolic state differences in the liver with hyperpolarized 13C spectroscopy and shows the ability to detect physiological perturbations in alanine aminotransferase activity, which is an encouraging result for future liver disease investigations with hyperpolarized magnetic resonance technology.

Hyperpolarized 13C Lactate, Pyruvate, and Alanine: Noninvasive Biomarkers for Prostate Cancer Detection and Grading​

An extraordinary new technique using hyperpolarized 13C-labeled pyruvate and taking advantage of increased glycolysis in cancer has the potential to improve the way magnetic resonance imaging is used for detection and characterization of prostate cancer. The aim of this study was to quantify, for the first time, differences in hyperpolarized [1-13C] pyruvate and its metabolic products between the various histologic grades of prostate cancer using the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Fast spectroscopic imaging techniques were used to image lactate, alanine, and total hyperpolarized carbon (THC = lactate + pyruvate + alanine) from the entire abdomen of normal mice and TRAMP mice with low- and high-grade prostate tumors in 14 s. Within 1 week, the mice were dissected and the tumors were histologically analyzed. Hyperpolarized lactate SNR levels significantly increased (P < 0.05) with cancer development and progression (41 ± 11, 74 ± 17, and 154 ± 24 in normal prostates, low-grade primary tumors, and high-grade primary tumors, respectively) and had a correlation coefficient of 0.95 with the histologic grade. In addition, there was minimal overlap in the lactate levels between the three groups with only one of the seven normal prostates overlapping with the low-grade primary tumors. The amount of THC, a possible measure of substrate uptake, and hyperpolarized alanine also increased with tumor grade but showed more overlap between the groups. In summary, elevated hyperpolarized lactate and potentially THC and alanine are noninvasive biomarkers of prostate cancer presence and histologic grade that could be used in future three-dimensional 13C spectroscopic imaging studies of prostate cancer patients​

In Vivo 13Carbon Metabolic Imaging at 3T With Hyperpolarized 13C-1-Pyruvate​

We present for the first time dynamic spectra and spectroscopic images acquired in normal rats at 3T following the injection of (13)C-1-pyruvate that was hyperpolarized by the dynamic nuclear polarization (DNP) method. Spectroscopic sampling was optimized for signal-to-noise ratio (SNR) and for spectral resolution of (13)C-1-pyruvate and its metabolic products (13)C-1-alanine, (13)C-1-lactate, and (13)C-bicarbonate. Dynamic spectra in rats were collected with a temporal resolution of 3 s from a 90-mm axial slab using a dual (1)H-(13)C quadrature birdcage coil to observe the combined effects of metabolism, flow, and T(1) relaxation. In separate experiments, spectroscopic imaging data were obtained during a 17-s acquisition of a 20-mm axial slice centered on the rat kidney region to provide information on the spatial distribution of the metabolites. Conversion of pyruvate to lactate, alanine, and bicarbonate occurred within a minute of injection. Alanine was observed primarily in skeletal muscle and liver, while pyruvate, lactate, and bicarbonate concentrations were relatively high in the vasculature and kidneys. In contrast to earlier work at 1.5 T, bicarbonate was routinely observed in skeletal muscle as well as the kidney and vasculature​

Double spin-echo sequence for rapid spectroscopic imaging of hyperpolarized 13C

Dynamic nuclear polarization of metabolically active compounds labeled with 13C has been introduced as a means for imaging metabolic processes in vivo. To differentiate between the injected compound and the various metabolic products, an imaging technique capable of separating the different chemical-shift species must be used. In this paper, the design and testing of a pulse sequence for rapid magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C is presented. The pulse sequence consists of a small-tip excitation followed by a double spin echo using adiabatic refocusing pulses and a ‘‘flyback’’ echo-planar readout gradient. Key elements of the sequence are insensitivity to calibration of the transmit gain, the formation of a spin echo giving high-quality spectral information, and a small effective tip angle that preserves the magnetization for a sufficient duration. Experiments in vivo showed three-dimensional coverage with excellent spectral quality and SNR.

Hyperpolarized C‐13 spectroscopic imaging of the TRAMP mouse at 3T—Initial experience

The transgenic adenocarcinoma of mouse prostate (TRAMP) mouse is a well‐studied murine model of prostate cancer with histopathology and disease progression that mimic the human disease. To investigate differences in cellular bioenergetics between normal prostate epithelial cells and prostate tumor cells, in vivo MR spectroscopic (MRS) studies with non‐proton nuclei, such as 13C, in the TRAMP model would be extremely useful. The recent development of a method for retaining dynamic nuclear polarization (DNP) in solution permits high signal‐to‐noise ratio (SNR) 13C MRI or MRSI data to be obtained following injection of a hyperpolarized 13C agent. In this transgenic mouse study, this method was applied using a double spin‐echo (DSE) pulse sequence with a small‐tip‐angle excitation RF pulse, hyperbolic‐secant refocusing pulses, and a flyback echo‐planar readout trajectory for fast (10–14 s) MRSI of 13C pyruvate (pyr) and its metabolic products at 0.135 cm3 nominal spatial resolution. Elevated 13C lactate (lac) was observed in both primary and metastatic tumors, demonstrating the feasibility of studying cellular bioenergetics in vivo with DNP hyperpolarized 13C MRSI.

Using the axis of rotation of polar navigator echoes to rapidly measure 3D rigid-body motion


An improved technique to prospectively correct three-dimensional rigid-body motion using polar spherical navigator (pNAV) echoes is presented. The technique is based on acquiring pNAVs of an object in a baseline and rotated position and determining the axis of rotation (AOR) between data sets, thereby reducing 3D rotations to a 2D, planar rotation. Finding the AOR is simplified by prerotating the baseline trajectory, which forces the axis to lie within a specific polar region of a spherical shell in k-space. Orbital navigator echoes are interpolated from the pNAV data in planes orthogonal to the AOR and cross-correlated to determine the 2D rotation. The rotation about the AOR is used in conjunction with its orientation to calculate the overall 3D rotation. The pNAV-AOR technique was tested for its precision, accuracy, and processing speed in detecting compound rotations and translations of varying magnitude. In comparison to the spherical navigator echo technique, the pNAV-AOR technique is noniterative, fast, and independent of rotation magnitude and direction. At low SNR, the technique can detect compound rotations to 0.5 degrees accuracy in an estimated 100 msec, indicating that prospective 3D rigid-body motion correction may be feasible with this technique.


Relationship between Caffeine-Induced Changes in Resting Cerebral Perfusion and Blood Oxygenation Level-Dependent Signal   


 Recent interest has emerged in the use of pharmacologic methods to maximize blood oxygenation level-dependent (BOLD) signal intensity changes in functional MR imaging (fMRI). Adenosine antagonists, such as caffeine and theophylline, have been identified as potential agents for this purpose. The present study was designed to determine whether caffeine-induced decreases in cerebral perfusion result in enhanced BOLD responses to visual and auditory stimuli. MR imaging was used to measure resting cerebral perfusion and stimulus-induced BOLD signal intensity changes in 19 patients. We evaluated the relationship between resting cerebral perfusion and the magnitude of BOLD signal intensity induced by visual and auditory stimulation under caffeine and placebo conditions. The data showed that changes in resting cerebral perfusion produced by caffeine are not a consistent predictor of BOLD signal intensity magnitude. Although all cerebral perfusion was reduced in all study participants in response to caffeine, only 47% of the participants experienced BOLD signal intensity increase. This finding was independent of the participants’ usual caffeine consumption. Therefore, the data presented shows that the relationship between resting cerebral perfusion and the magnitude of BOLD signal intensity is complex. It is not possible to consistently enhance BOLD signal intensity magnitude by decreasing resting perfusion with caffeine. Future studies aimed at evaluating the relationship between perfusion and BOLD signal intensity changes should seek a means to selectively modulate known components of the neural and vascular responses independently.


Laurienti PJ et al. Am J Neuroradiol. 2003;24(8):1607-1611.     


Peripheral nerve stimulation properties of head and body gradient coils of various sizes   

 Peripheral nerve stimulation (PNS) caused by time-varying magnetic fields has been studied both theoretically and experimentally. A human volunteer study performed on three different body-size gradient coils and one head-size gradient coil is presented in this work. The experimental results were used to generate average PNS threshold parameters for the tested gradient systems. It was found that the average stimulation threshold increases while gradient-region-of-uniformity size decreases. In addition, linear relationships between PNS parameters and diameter of homogeneous gradient spherical volume (DSV) were discovered: SR(min) and DeltaG(min) both vary inverse linearly with DSV. More importantly, the chronaxie value was found to vary inversely linearly with the DSV. This finding indicates that, contrary to the general understanding, the parameter “chronaxie” in the commonly accepted simple stimulation models cannot be considered to be a single-value, nerve-specific constant. A modified linear model for gradient-induced PNS based on these results was developed, which may permit, for the first time, the general prediction of nerve stimulation properties for gradient coils of arbitrary linear region dimension.

Neural correlates of interindividual differences in the subjective experience of pain             


Some individuals claim that they are very sensitive to pain, whereas others say that they tolerate pain well. Yet, it is difficult to determine whether such subjective reports reflect true interindividual experiential differences. Using psychophysical ratings to define pain sensitivity and functional magnetic resonance imaging to assess brain activity, we found that highly sensitive individuals exhibited more frequent and more robust pain-induced activation of the primary somatosensory cortex, anterior cingulate cortex, and prefrontal cortex than did insensitive individuals. By identifying objective neural correlates of subjective differences, these findings validate the utility of introspection and subjective reporting as a means of communicating a first-person experience.


Coghill RC et al. Proc Natl Acad Sci USA. 2003;100(14):8538-8542          

Diffusion anisotropy in the corpus callosum 


The corpus callosum is a heterogeneous white-matter tract that connects the cerebral hemispheres. The purpose of this investigation was to study its microstructural architecture in normal human adult brains by using diffusion tensor imaging (DTI). Two hundred consecutive patients referred for brain MR imaging underwent additional DTI with a high gradient field strength applied in six directions. Forty-two patients met the following inclusion criteria: 1) normal brain and 2) age greater than 18 years. Anisotropy maps were generated, and regions of interest were drawn around specified regions within the corpus callosum. Results were stratified by sex and age. In addition, available histologic specimens of the corpus callosum from cadaver brains were analyzed with conventional and specialized vascular staining. Results concluded that the anisotropy values in the various regions of the corpus callosum differed significantly. Average values of the anisotropy index for the genus, body, and splenium of the corpus callosum were 0.400, 0.456, and 0.539, respectively. The differences between these values proved to be statistically significant (P <.01), and the results of this investigation show a statistically significant increase in anisotropy of the corpus callosum in its more posterior portions compared with its more anterior portions across sex and age groups. Although the microstructural etiology for this is apparent, increase in anisotropy is unclear due to the number of possible mechanisms presented.

Test-retest reproducibility of quantitative CBF measurements using FAIR perfusion MRI and acetazolamide challenge 


The reproducibility of quantitative cerebral blood flow (CBF) measurements using MRI with arterial spin labeling and acetazolamide challenge was assessed in 12 normal subjects, each undergoing the identical experimental procedure on two separate days. CBF was measured on a 1.5T scanner using a flow-sensitive alternating inversion recovery (FAIR) pulse sequence, performed both at baseline and 12 min after intravenous administration of acetazolamide. T(1) was measured in conjunction with the FAIR scan in order to calculate quantitative CBF. The CBF maps were segmented to separate gray matter (GM) from white matter (WM) for region-of-interest (ROI) analyses. Post- acetazolamide CBF values (ml/100 g/min, mean +/- SD) of 87.5 +/- 12.5 (GM) and 46.1 +/- 10.8 (WM) represented percent increases of 37.7% +/- 24.4% (GM) and 40.1% +/- 24.4% (WM). Day-to-day differences in baseline CBF were -1.7 +/- 6.9 (GM) and -1.4 +/- 4.7 (WM) or, relative to the mean CBF over both days for each subject, -2.5% +/- 11.7% (GM) and -3.8% +/- 13.6% (WM) Day- to-day differences in absolute post-ACZ CBF increase were -2.5 +/- 6.8 (GM) and 2.7 +/- 9.4 (WM) or, relative to the mean CBF increase over both days for each subject, -4.7% +/- 13.3% (GM) and 9.1% +/- 26.2% (WM). Thus, FAIR- based CBF measurements show satisfactory reproducibility from day to day, but with sufficient variation to warrant caution in interpreting longitudinal data. The hemispheric asymmetry of baseline CBF and post-acetazolamide CBF increases varied within a narrower range and should be sensitive to small changes related to disease or treatment.


Yen YF et al. Magn Reson Med. 2002;47(5):921-928 

High b-value diffusion-weighted MRI of normal brain      


As MR scanner hardware has improved and gradient strengths have increased, we are able to generate higher b values for diffusion-weighted (DW) imaging. Our purpose was to evaluate the appearance of the normal brain on DW MR images as the diffusion gradient strength (“b value”) is increased from 1,000 to 3,000 s/mm2. In order to do this three sets of echo planar images were acquired at 1.5 T in 25 normal subjects using progressively increasing strengths of a diffusion-sensitizing gradient (corresponding to b values of 0, 1,000, and 3,000 s/mm2). All other imaging parameters remained constant, and qualitative assessments of trace images were supplemented by quantitative measures of MR signal and noise in eight different anatomic regions. As a result, gradient strength increased from b = 1,000 to 3,000, both gray and white matter structures diminished in signal as expected based on their relative diffusion coefficients, and the signal-to-noise ratios for the b = 1,000 images were approximately 2.2 times higher than for the b = 3,000 images (p < 0.0001). As the strength of the diffusion-sensitizing gradient increased, white matter became progressively hyperintense to gray matter. Brain DW images obtained at b = 3,000 appeared significantly different from those obtained at b = 1,000, reflecting expected loss of signal from all areas of the brain in proportion to their ADC values. Consequently, when all other imaging parameters are held constant, b = 3,000 DW images appear significantly noisier than b = 1,000 images, and white matter tracts are significantly more hyperintense than gray matter structures.

Burdette JH et al. J Comput Assist Tomogr. 2001;25(4):515-519            

Dynamic breast MRI with spiral trajectories: 3D versus 2D     


A three-dimensional (3)D spiral sequence was developed for dynamic breast magnetic resonance (MR) imaging with much improved image quality. Partial Z phase encoding was applied to obtain thinner slices for a coverage of the whole breast. Comparison between the 3D and a previously developed multi-slice 2D spiral sequences was performed on ten healthy volunteers without contrast and five breast patients with gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA). The 3D spiral images had significantly less off-resonance blurring and spiral artifacts. With a small compromise on temporal resolution (7.7 seconds in 2D and 10.6 seconds in 3D), we obtained 32 interpolated 3-5 mm slices (with 20 Z phase encodes) for a full coverage of 10-16 cm breast with the same 1 x 1 mm2 in-plane resolution as the 2D sequence, which had 12 8-13 mm slices. Contrast between glandular and soft tissue in normal breasts was increased by about 25%. The reduced repetition time in the 3D spiral acquisition led to an increased Gd-enhanced signal. The difference between the enhancement of malignant and benign lesions increased by sevenfold. We expect that this new development could lead to improved specificity in characterizing breast lesions using MR imaging.


Yen YF et al. J Magn Reson Imaging. 2001;11:351-359     



Diffusion and perfusion MR imaging of cerebral ischemia        



Diffusion and perfusion magnetic resonance (MR) imaging methods have found increasing use for monitoring the effects of cerebral ischemia under clinical and experimental conditions. Blood perfusion can be visualized by either studying the patency of the cerebrovascular bed, recording exchange of diffusible tracers between blood and brain, or measuring the volume and transit time of the circulating blood. Diffusion imaging is based on the modulation of signal intensity by brain water diffusion, and by recording a series of diffusion-weighted images, calculations of the apparent diffusion coefficient (ADC) and the reconstruction of quantitative ADC images can be produced. Brain ADC changes are a sensitive marker of ionic equilibrium, and since disturbances of ion and water homeostasis are among the first pathological alterations induced by brain ischemia, diffusion imaging is able to detect the incipient injury within minutes. Conversely, the reversal of these alterations is able to detect the incipient injury within minutes, and is an early and reliable predictor of postischemic recovery. 




Baker MD et al. Ann Thorac Surg. 2000;70(5):1795-1795.              

False cerebral activation on BOLD functional MR images: study of low-amplitude motion weakly correlated to stimulus 


Movements of the participant during blood oxygen level-dependent (BOLD) functional MR imaging cerebral activation studies are known to occasionally produce regions of false activation when they are relatively large (>3 mm) and highly correlated with the stimulus. We investigated whether minimal (<1 mm), weakly correlated movements in a controlled functional MR imaging model could produce false activation artifacts that could potentially mimic regions of true activation in size, location, and statistical significance. In order to determine this a life-size brain phantom was constructed. Imaging was performed at 1.5 T using a 2D spiral sequence. Controlled, in-plane, submillimeter movements of the phantom were generated and were made to correlate with a hypothetical “boxcar” stimulus over the range 0.31 < r < 0.96. Regions of false activation were sought using standard statistical methods (SPM96). Results were obtained through a pneumatic system which provided motion control with average in-plane displacements and rotations of 0.74 mm and 0.47 degrees. 18 datasets were analyzed for a statistical threshold of P = .001, with a median number of 3.5 for falsely activated regions, and a mean size of 71.7 voxels. Areas of possibly false activation of average size 72.5 voxels resulting from passive motion of the resting human participant were observed in two of four experiments. Therefore, participant movements of 1 mm or less that are only modestly correlated with a blocked stimulus paradigm can produce appreciable false activation artifacts on BOLD functional MR imaging studies, even when strict image realignment methods are used to prevent them.



Field AS et al. Am J Neuroradiol. 2000;21(8):1388-1396.  

 Breast disease: dynamic spiral MR imaging. Radiology  


The purpose of this study was to compare various subjective, empiric, and pharmacokinetic methods for interpreting findings at dynamic magnetic resonance (MR) imaging of the breast. Dynamic spiral breast MR imaging was performed in 52 women with, or suspected of having breast disease. Gadolinium-enhanced images were obtained at 12 locations through the whole breast every 7.8 seconds for 8.5 minutes after bolus injection of contrast material. Time-signal intensity curves from regions of interest corresponding to 57 pathologically proved lesions were analyzed by means of a two-compartment pharmacokinetic model, and the diagnostic performance of various parameters was analyzed. Findings included invasive carcinoma in 17 patients, isolated ductal carcinoma in situ (DCIS) in six, and benign lesions in 34. Although some overlap between carcinomas and benign diagnoses was noted for all parameters, receiver operating characteristic analysis indicated that the exchange rate constant had the greatest overall ability to discriminate benign and malignant disease. Dynamic spiral breast MR imaging proved an excellent method with which to collect contrast enhancement data rapidly enough that accurate comparisons can be made between many analytic methods.

Daniel BL et al. Radiology. 1998;209:499-509.