Jonas Svensson

Reduced field‐of‐view MRI using outer volume suppression for spinal cord diffusion imaging

A spin‐echo single‐shot echo‐planar imaging (SS‐EPI) technique with a reduced field of view (FOV) in the phase‐encoding direction is presented that simultaneously reduces susceptibility effects and motion artifacts in diffusion‐weighted (DW) imaging (DWI) of the spinal cord at a high field strength (3T). To minimize aliasing, an outer volume suppression (OVS) sequence was implemented. Effective fat suppression was achieved with the use of a slice‐selection gradient‐reversal technique. The OVS was optimized by numerical simulations with respect to T1 relaxation times and B1 variations. The optimized sequence was evaluated in vitro and in vivo. In simulations the optimized OVS showed suppression to <0.25% and ∼3% in an optimal and worst‐case scenario, respectively. In vitro measurements showed a mean residual signal of <0.95% ± 0.42 for all suppressed areas. In vivo acquisition with 0.9 × 1.05 mm2 in‐plane resolution resulted in artifact‐free images. The short imaging time of this technique makes it promising for clinical studies. Magn Reson Med 57:625–630, 2007.

Quantitative measurement of regional lung ventilation using 3He MRI.

A new strategy for a quantitative measurement of regional pulmonary ventilation using hyperpolarized helium‐3 (3He) MRI has been developed. The method employs the build‐up of the signal intensity after a variable number of 3He breaths. A mathematical model of the signal dynamics is presented, from which the local ventilation, defined as the fraction of gas exchanged per breath within a given volume, is calculated. The model was used to create ventilation maps of coronal slices of guinea pig lungs. Ventilation values very close to 1 were found in the trachea and the major airways. In the lung parenchyma, regions adjacent to the hilum showed values of 0.6–0.8, whereas 0.2–0.4 was measured in peripheral regions. Monte Carlo simulations were used to investigate the accuracy of the method and its limitations. The simulations revealed that, at presently attainable signal‐to‐noise ratios, the ventilation parameter can be determined with a relative uncertainty of <5% over a wide range of values. Magn Reson Med 48:223–232, 2002.

dGEMRIC (delayed gadolinium-enhanced MRI of cartilage) indicates adaptive capacity of human knee cartilage.

Delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC) is a new imaging technique to estimate joint cartilage glycosaminoglycan content by T1‐relaxation time measurements after penetration of the hydrophilic contrast agent Gd‐DTPA2‐. This study compares dGEMRIC in age‐matched healthy volunteers with different levels of physical activity: Group 1 (n = 12): nonexercising individuals; Group 2 (n = 16): individuals with physical exercise averaging twice weekly; Group 3 (n = 9): male elite runners. dGEMRIC was performed 2 hr after an intravenous injection of Gd‐DTPA2‐ at 0.3 mmol/kg body weight. T1 differed significantly between the three different levels of physical exercise. T1 values (mean of medial and lateral femoral cartilage) for Groups 1, 2, and 3 were: 382 ± 33, 424 ± 22 and 476 ± 36, respectively (ms, mean ± SD) (P = 0.0004, 1 vs. 2 and 0.0002, 2 vs. 3). Irrespective of the exercise level, T1 was longer in lateral compared to medial femoral cartilage (P = 0.00005; n = 37). In conclusion, this cross‐sectional study indicates that human knee cartilage adapts to exercise by increasing the glycosaminoglycan content. Furthermore, results suggest a compartmental difference within the knee with a higher glycosaminoglycan content in lateral compared to medial femoral cartilage. A higher proportion of extracellular water, i.e., larger distribution volume, may to some extent explain the high T1 in the elite runners. Magn Reson Med 51:286–290, 2004.

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.

Deaths Among Adult Patients With Hypopituitarism : Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality

CONTEXT Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified. OBJECTIVE To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up. DESIGN AND METHODS All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed. MAIN OUTCOME MEASURES Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up. RESULTS An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy. CONCLUSION Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.

Cerebral perfusion assessment by bolus tracking using hyperpolarized 13C.

Cerebral perfusion was assessed with 13C MRI in a rat model after intravenous injections of the 13C‐labeled compound bis‐1,1‐(hydroxymethyl)‐1‐13C‐cyclopropane‐D8 in aqueous solutions hyperpolarized by dynamic nuclear polarization (DNP). Since the tracer acted as a direct signal source, several of the problems associated with techniques based on traditional dynamic susceptibility contrast (DSC) MRI contrast agents were avoided. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were calculated. The MTT was determined to be 2.8 ± 0.8 sec. However, arterial partial‐volume effects in the animal model prevented accurate absolute quantification of CBF and CBV. It was demonstrated that depolarization of the hyperpolarized 13C tracer via relaxation and the imaging sequence had little influence on CBF assessment when the time resolution of the imaging sequence was short compared to the MTT. However, CBV and MTT were increasingly underestimated as MTT or the depolarization rate increased if depolarization was not taken into account. With a modified bolus‐tracking theory depolarization could be compensated for, assuming that the depolarization rate was known. Three separate compensation methods were investigated experimentally and by numerical simulations. Magn Reson Med 51:464–472, 2004.

Influence of Chironomus plumosus larvae on ammonium flux and denitrification (measured by the acetylene blockage- and the isotope pairing-technique) in eutrophic lake sediment

Oxygen uptake, ammonium flux and denitrification were determined insediment from a eutrophic lake in southern Sweden. Part of the sediment wasbioturbated by incubation in a laboratory mesocosm by incubation containing2000 tube-dwelling larvae of Chironomus plumosus L. m−2.Oxygen consumption was increased 2-fold in the bioturbated compared with thenonbioturbated sediment, some 20% of the increase could be explainedby chironomid respiration. There was a net release of ammonium from thebioturbated sediment to the overlying water. Only 11–45% ofthis could be explained on the basis of larval excretion. With increasingnitrate concentration, denitrification of the nitrate coming from the water(dw) increased to a greater extent in the bioturbated than in thenon-bioturbated sediment, whereas denitrification of the nitrate from thecoupled nitrification-denitrification (dn) was unaffected. The acetyleneblockage technique underestimated denitrification by 63–88%compared with the nitrogen isotope pairing technique. The results indicatethat bioturbation by tube-dwelling chironomid larvae can have a major impacton the nitrogen turnover in lake sediment, mobilising the ammonium to thewater and stimulating denitrification by reducing the diffusive barrierblocking nitrate from reaching anoxic zones in the sediment. Under theaerobic conditions under which the experiments were conducted, thebioturbated eutrophic sediment acted as a more pronounced sink for inorganicnitrogen compared with the non-bioturbated sediment.

Image artifacts due to a time-varying contrast medium concentration in 3D contrast-enhanced MRA.

The purpose of this work was to study image effects due to time‐varying contrast medium concentration in contrast‐enhanced three dimensional (3D) magnetic resonance angiography (MRA) images. Two different simulation models (1D and 3D) and two different contrast medium variation schemes were used. Phantom measurements were also performed. Experiments were performed for several different bolus timings. Similar sequence and image object parameters were used in both simulations and measurements (TE/TR 2.1/7.8 mses, flip angle 30°, T1/T2 1200‐80/150‐40 msec, flow velocity 100 cm/sec). A small variation in bolus timing yielded large variations in the appearance of the image effects, especially if the center of k‐space was sampled in the vicinity of rapid contrast medium concentration variation. For a typical bolus injection in a patient, a severe signal loss but only minor ringing and edge artifacts appeared if the bolus injection was poorly timed. Effects of pulsatile flow were minor. The 3D model proved to be a useful tool in these studies. J. Magn. Reson. Imaging 1999;10:919–928.

Longitudinal assessment of femoral knee cartilage quality using contrast enhanced MRI (dGEMRIC) in patients with anterior cruciate ligament injury - comparison with asymptomatic volunteers.

OBJECTIVE In this observational longitudinal study we estimate knee joint cartilage glycosaminoglycan (GAG) content, in patients with an acute anterior cruciate ligament (ACL) injury, with or without a concomitant meniscus injury. METHODS 29 knees (19 men/10 women) were prospectively examined by repeat delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), approximately 3 weeks and 2.3±1.3 (range 4.5) years after the injury. We estimated the GAG content (T1Gd) in the central weight-bearing parts of the medial and lateral femoral cartilage and compared results with a reference cohort (n=24) with normal knees and no history of injury examined by dGEMRIC at one occasion previously. RESULTS The healthy reference group had longer T1Gd values compared with the ACL-injured patients at follow-up both medially: 428±38 vs 363±61ms (P<0.0001) and laterally: 445±41 vs 396±48ms (P=0.0002). At follow-up T1Gd was lower in meniscectomized patients compared to those without a meniscectomy, both medially (-84ms, P=0.002) and laterally (-38ms, P=0.05). In the injured group, the medial femoral cartilage showed similar T1Gd at the two dGEMRIC investigations: 357±50 vs 363±61ms (P=0.57), whereas the lateral femoral cartilage T1Gd increased: 374±48 vs 396±48ms (P=0.04). CONCLUSIONS The general decrease in cartilage T1Gd in ACL-injured patients compared with references provide evidence for structural matrix GAG changes that seem more pronounced if a concomitant meniscal injury is present. The fact that post-traumatic OA commonly develops in ACL-injured patients, in particularly those with meniscectomy, suggests that shorter T1Gd may be an early biomarker for OA.

Rapid cortical reorganisation and improved sensitivity of the hand following cutaneous anaesthesia of the forearm.

The cortical representation of various body parts constantly changes based on the pattern of afferent nerve impulses. As peripheral nerve injury results in a cortical and subcortical reorganisation this has been suggested as one explanation for the poor clinical outcome seen after peripheral nerve repair in humans. Cutaneous anaesthesia of the forearm in healthy subjects and in patients with nerve injuries results in rapid improvement of hand sensitivity. The mechanism behind the improvement is probably based on a rapid cortical and subcortical reorganisation. The aim of this work was to study cortical changes following temporary cutaneous forearm anaesthesia. Ten healthy volunteers participated in the study. Twenty grams of a local anaesthetic cream (EMLA®) was applied to the volar aspect of the right forearm. Functional magnetic resonance imaging was performed during sensory stimulation of all fingers of the right hand before and during cutaneous forearm anaesthesia. Sensitivity was also clinically assessed before and during forearm anaesthesia. A group analysis of functional magnetic resonance image data showed that, during anaesthesia, the hand area in the contralateral primary somatosensory cortex expanded cranially over the anaesthetised forearm area. Clinically right hand sensitivity in the volunteers improved during forearm anaesthesia. No significant changes were seen in the left hand. The clinically improved hand sensitivity following forearm anaesthesia is probably based on a rapid expansion of the hand area in the primary somatosensory cortex which presumably results in more nerve cells being made available for the hand in the primary somatosensory cortex.