Lars E. Olsson

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) in early knee osteoarthritis.

Delayed contrast‐enhanced MRI of cartilage (dGEMRIC) is a noninvasive technique to study cartilage glycosaminoglycan (GAG) content in vivo. This study evaluates dGEMRIC in patients with preradiographic degenerative cartilage changes. Seventeen knees in 15 patients (age 35–70) with arthroscopically verified cartilage changes (softening and fibrillations) in the medial or lateral femoral compartment, knee pain, and normal weight‐bearing radiography were included. MRI (1.5 T) was performed precontrast and at 1.5 and 3 hr after an intravenous injection of Gd‐DTPA2− at 0.3 mmol/kg body weight. T1 measurements were made in regions of interest in medial and lateral femoral cartilage using sets of five turbo inversion recovery images. Precontrast, R1 (R1 = 1/T1, 1/s) was slightly lower in diseased compared to reference compartment, indicating increased hydration (P = 0.01). Postcontrast, R1 was higher in diseased than in reference compartment at 1.5 hr, 3.45 ± 0.90 and 2.64 ± 0.58 (mean ± SD), respectively (P < 0.01), as well as at 3 hr, 2.94 ± 0.60 and 2.50 ± 0.37, respectively (P = 0.01). The washout of the contrast medium was faster in diseased cartilage as shown by a higher R1 at 1.5 than at 3 hr in the diseased but not in the reference compartment. In conclusion, dGEMRIC can identify GAG loss in early stage cartilage disease with a higher sensitivity at 1.5 than 3 hr. Magn Reson Med 49:488–492, 2003.

Gd-DTPA2)-enhanced MRI of femoral knee cartilage: a dose-response study in healthy volunteers

The negatively charged contrast agent Gd‐DTPA2– distributes inversely to the cartilage fixed charged density. This enables structural cartilage examinations by contrast‐enhanced MRI. In line with the development of a clinically applicable protocol for such examinations, this study describes the temporal pattern of Gd‐DTPA2– distribution in femoral knee cartilage at three different doses in healthy volunteers. Nineteen volunteers (ages 21–28 years) were examined with a 1.5T MRI system. Quantitative relaxation rate measurements were made in weight‐bearing central parts of femoral cartilage using sets of five turbo inversion recovery images with different inversion times. The cartilage was analyzed before and four times (1–4 h) after an intravenous injection of Gd‐DTPA2– at single, double, and triple doses: 0.1, 0.2, and 0.3 mmol/kg body weight, respectively. The increase in R1 postcontrast was linearly dose‐related at all times. The highest R1 values were registered at 2 and 3 h postcontrast, suggesting 2 h to be optimal in the clinical situation. The triple dose indicated a subtle compartmental difference in men, with higher contrast distribution medially than laterally. Results suggest that the triple dose is needed to detect minor cartilage matrix differences. Magn Reson Med 46:1067–1071, 2001.

Ferrous sulphate gels for determination of absorbed dose distributions using MRI technique: basic studies

Two gels have been found to be suitable to load with ferrous sulphate solution. In these soft tissue equivalent phantoms, the absorbed dose distribution can be measured after irradiation in clinically used MR imaging equipment. The present studies were carried out using a 0.25 T NMR analyser without imaging properties. A ferrous sulphate solution, 0.05 M with respect to sulphuric acid, can be gelled with 4% gelatin to give a dosemeter which has a response which is linearly correlated (r = 0.998) with the absorbed dose in the interval 0-40 Gy. Ferrous sulphate solution can also be gelled with 1% agarose, but this gel has to be purged with oxygen to obtain a linear relationship (r = 0.997) in the same absorbed dose interval. The ferrous sulphate loaded gels have a sensitivity which is a factor of 2.2 or 4.0 times higher for gelatin and agarose, respectively, than the ordinary dosemeter solution. Because the standard deviation of background measurements is higher for the gels than for the dosemeter solution, the minimum detectable absorbed dose is about the same, or 1.0 Gy, for the two gels and the dosemeter solution. The sensitivity of the ferrous sulphate loaded gels shows no dependence on dose rate if the mean dose rate and the absorbed dose per pulse are within the limits normally used by accelerators for radiotherapy.

Hyperpolarized 13C MR angiography using trueFISP.

A 13C‐enriched water‐soluble compound (bis‐1,1‐(hydroxymethyl)‐1‐13C‐cyclopropane‐D8), with a 13C‐concentration of approximately 200 mM, was hyperpolarized to ∼15% using dynamic nuclear polarization, and then used as a contrast medium (CM) for contrast‐enhanced magnetic resonance angiography (CE‐MRA). The long relaxation times (in vitro: T1 ≈ 82 s, T2 ≈ 18 s; in vivo: T1 ≈ 38 s, T2 ≈ 1.3 s) are ideal for steady‐state free precession (SSFP) imaging with a true fast imaging and steady precession (trueFISP) pulse sequence. It was shown both theoretically and experimentally that the optimal flip angle was 180°. CE‐MRA was performed in four anesthetized live rats after intravenous injection of 3 ml CM. The angiograms covered the thoracic/abdominal region in two of the animals, and the head‐neck region in the other two. Fifteen consecutive images were acquired in each experiment, with a flip‐back pulse at the end of each image acquisition. In the angiograms, the vena cava (SNR ≈ 240), aorta, renal arteries, carotid arteries (SNR ≈ 75), jugular veins, and several other vessels were visible. The SNR in the cardiac region was 500. Magnetization was preserved from one image acquisition to the next using the flip‐back technique (SNRcardiac ≈ 10 in the 15th image). Magn Reson Med 50:256–262, 2003.

MRI-guided thermal therapy of transplanted tumors in the canine prostate using a directional transurethral ultrasound applicator

To evaluate MRI‐based techniques for visual guidance, thermal monitoring, and assessment during transurethral ultrasound thermal therapy of implanted tumors in an in vivo canine prostate model.

MAGIC-type polymer gel for three-dimensional dosimetry: Intensity-modulated radiation therapy verification

A new type of polymer gel dosimeter, which responds well to absorbed dose even when manufactured in the presence of normal levels of oxygen, was recently described by Fong et al. [Phys. Med. Biol. 46, 3105-3113 (2001)] and referred to by the acronym MAGIC. The aim of this study was to investigate the feasibility of using this new type of gel for intensity-modulated radiation therapy (IMRT) verification. Gel manufacturing was carried out in room atmosphere under normal levels of oxygen. IMRT inverse treatment planning was performed using the Helios software. The gel was irradiated using a linear accelerator equipped with a dynamic multileaf collimator, and intensity modulation was achieved using sliding window technique. The response to absorbed dose was evaluated using magnetic resonance imaging. Measured and calculated dose distributions were compared with regard to in-plane isodoses and dose volume histograms. In addition, the spatial and dosimetric accuracy was evaluated using the gamma formalism. Good agreement between calculated and measured data was obtained. In the isocenter plane, the 70% and 90% isodoses acquired using the different methods are mostly within 2 mm, with up to 3 mm disagreement at isolated points. For the planning target volume (PTV), the calculated mean relative dose was 96.8 +/- 2.5% (1 SD) and the measured relative mean dose was 98.6 +/- 2.2%. Corresponding data for an organ at risk was 34.4 +/- 0.9% and 32.7 +/- 0.7%, respectively. The gamma criterion (3 mm spatial/3% dose deviation) was fulfilled for 94% of the pixels in the target region. Discrepancies were found in hot spots the upper and lower parts of the PTV, where the measured dose was up to 11% higher than calculated. This was attributed to sub optimal scatter kernels used in the treatment planning system dose calculations. Our results indicate great potential for IMRT verification using MAGIC-type polymer gel.

Linear energy transfer dependence of a normoxic polymer gel dosimeter investigated using proton beam absorbed dose measurements

Three-dimensional dosimetry with good spatial resolution can be performed using polymer gel dosimetry, which has been investigated for dosimetry of different types of particles. However, there are only sparse data concerning the influence of the linear energy transfer (LET) properties of the radiation on the gel absorbed dose response. The purpose of this study was to investigate possible LET dependence for a polymer gel dosimeter using proton beam absorbed dose measurements. Polymer gel containing the antioxidant tetrakis(hydroxymethyl)phosphonium (THP) was irradiated with 133 MeV monoenergetic protons, and the gel absorbed dose response was evaluated using MRI. The LET distribution for a monoenergetic proton beam was calculated as a function of depth using the Monte Carlo code PETRA. There was a steep increase in the Monte Carlo calculated LET starting at the depth corresponding to the front edge of the Bragg peak. This increase was closely followed by a decrease in the relative detector sensitivity (Srel = Dgel/Ddiode), indicating that the response of the polymer gel detector was dependent on LET. The relative sensitivity was 0.8 at the Bragg peak, and reached its minimum value at the end of the proton range. No significant effects in the detector response were observed for LET < 4.9 keV microm(-1), thus indicating that the behaviour of the polymer gel dosimeter would not be altered for the range of LET values expected in the case of photons or electrons in a clinical range of energies.

Diffusion of ferric ions in agarose dosimeter gels

The diffusion of ferric ions produced by irradiation in a dosimeter gel, consisting of a ferrous sulphate solution and agarose gel, has been studied. The diffusion coefficient of ferric ions in the gel was found to be 1.91*10-2 cm2 h-1+or-5%. It was shown that the dose image obtained with an MR scanner deteriorates due to diffusion. This deterioration can be predicted with the aid of the measured diffusion coefficient. It was concluded that if the MR measurements (1/T1 image) of a typical depth-dose distribution are carried out within 2 hours of irradiation the diffusion will not have a significant effect on the results.

MR coronary angiography in pigs with intraarterial injections of a hyperpolarized (13)C substance.

A new diagnostic application of a water‐soluble contrast medium (CM) based on the hyperpolarization of a 13C substance is introduced. The degree of polarization achieved is >30%, which is about a factor of 105 higher than the thermal equilibrium polarization level at 1.5 T. Imaging of hyperpolarized (HP) CM during a cardiac interventional MRI procedure was studied. Catheters were positioned in the left and right coronary arteries of pigs. A coil tuned to 13C was used for nonproton imaging. The HP‐13C CM (∼5 ml, 0.5 M, ∼30% polarization) was injected during projection imaging using a fully balanced steady‐state free precession (SSFP) pulse sequence with and without cardiac gating. The contrast agent‐filled catheter was clearly visible during the procedure. The coronary arteries were well depicted and the signal‐to‐noise ratios (SNRs) were in the range of 10–40. The use of HP‐13C CM may provide a new diagnostic procedure for interventional MRI. Magn Reson Med, 2006.

Perfusion assessment with bolus differentiation: A technique applicable to hyperpolarized tracers.

A new technique for assessing tissue blood flow using hyperpolarized tracers, based on the fact that the magnetization of a hyperpolarized substance can be destroyed permanently, is described. Assessments of blood flow with this technique are inherently insensitive to arterial delay and dispersion, and allow for quantification of the transit time and dispersion in the arteries that supply the investigated tissue. Renal cortical blood flow was studied in six rabbits using a 13C‐labeled compound (2‐hydroxyethylacrylate) that was polarized by the parahydrogen‐induced polarization (PHIP) technique. The renal cortical blood flow was estimated to be 5.7/5.4 ± 1.6/1.3 ml/min per milliliter of tissue (mean ± SD, right/left kidney), and the mean transit time and dispersion in the renal arteries were determined to be 1.47/1.42 ± 0.07/0.07 s and 1.78/1.93 ± 0.40/0.42 s2, respectively. Magn Reson Med 52:1043–1051, 2004.