Freddy Ståhlberg

Pulsatile brain movement and associated hydrodynamics studied by magnetic resonance phase imaging

SummaryBrain tissue movements were studied in axial, sagittal and coronal planes in 15 healthy volunteers, using a gated spin echo MRI sequence. All movements had characteristics different from those of perfusion and diffusion. The highest velocities occurred during systole in the basal ganglia (maximum 1.0 mm/s) and brain stem (maximum 1.5 mm/s). The movements were directed caudally, medially and posteriorly in the basal ganglia, and caudally-anteriorly in the pons. Caudad and anterior motion increased towards the foramen magnum and towards the midline. The resultant movement occurred in a funnelshaped fashion as if the brain were pulled by the spinal cord. This may be explained by venting of brain and cerebrospinal fluid (CSF) through the tentorial notch and foramen magnum. The intracranial volume is assumed to be always constant by the Monro-Kellie doctrine. The intracranial dynamics can be viewed as an interplay between the spatial requirements of four main components: arterial blood, capillary blood (brain volume), venous blood and CSF. These components could be characterized, and the expansion of the arteries and the brain differentiated, by applying the Monro-Kellie doctrine to every moment of the cardiac cycle. The arterial expansion causes a remoulding of the brain that enables its piston-like action. The arterial expansion creates the prerequisites for the expansion of the brain by venting CSF to the spinal canal. The expansion of the brain is, in turn, responsible for compression of the ventricular system and hence for the intraventricular flow of CSF.

13C imaging-a new diagnostic platform.

The evolution of magnetic resonance imaging (MRI) has been astounding since the early 1980s, and a broad range of applications has emerged. To date, clinical imaging of nuclei other than protons has been precluded for reasons of sensitivity. However, with the recent development of hyperpolarization techniques, the signal from a given number of nuclei can be increased as much as 100,000 times, sufficient to enable imaging of nonproton nuclei. Technically, imaging of hyperpolarized nuclei offers several unique properties, such as complete lack of background signal and possibility for local and permanent destruction of the signal by means of radio frequency (RF) pulses. These properties allow for improved as well as new techniques within several application areas. Diagnostically, the injected compounds can visualize information about flow, perfusion, excretory function, and metabolic status. In this review article, we explain the concept of hyperpolarization and the techniques to hyperpolarize 13C. An overview of results obtained within angiography, perfusion, and catheter tracking is given, together with a discussion of the particular advantages and limitations. Finally, possible future directions of hyperpolarized 13C MRI are pointed out.

Assessment of regional cerebral blood flow by dynamic susceptibility contrast MRI using different deconvolution techniques

Regional cerebral blood flow (rCBF) was assessed using dynamic susceptibility‐contrast MRI at 1.5 T. A simultaneous dual FLASH pulse sequence and Gd‐DTPA‐BMA (0.3 mmol/kg b.w.) were used for examination of 43 volunteers, measuring rCBF in frontal white matter (WM) and in gray matter in the thalamus (GM). Arterial input functions (AIFs) were registered 1) in the carotid artery and 2) in an artery within the GM/WM slice. The measured concentration‐vs.‐time curve was deconvolved with the AIF using both Fourier Transform (FT) and Singular Value Decomposition (SVD). Relative rCBF was given by the height of the deconvolved response curve. For each volunteer, eight different rCBF maps were calculated, representing different combinations of deconvolution techniques, AIFs, and filters. The average GM–WM rCBF ratios ranged from 2.0–2.2, depending on methodology. Absolute rCBF was 68 ± 28 ml/(min 100 g) in GM and 35 ± 13 ml/(min 100g) in WM (mean ± SD, n = 39). GM–WM rCBF ratios obtained using SVD were 6–10% higher than corresponding ratios obtained using FT. Magn Reson Med 43:691–700, 2000.

7-T MR-from research to clinical applications?

Over 20 000 MR systems are currently installed worldwide and, although the majority operate at magnetic fields of 1.5 T and below (i.e. about 70%), experience with 3‐T (in high‐field clinical diagnostic imaging and research) and 7‐T (research only) human MR scanners points to a future in functional and metabolic MR diagnostics. Complementary to previous studies, this review attempts to provide an overview of ultrahigh‐field MR research with special emphasis on emerging clinical applications at 7 T. We provide a short summary of the technical development and the current status of installed MR systems. The advantages and challenges of ultrahigh‐field MRI and MRS are discussed with special emphasis on radiofrequency inhomogeneity, relaxation times, signal‐to‐noise improvements, susceptibility effects, chemical shifts, specific absorption rate and other safety issues. In terms of applications, we focus on the topics most likely to gain significantly from 7‐T MR, i.e. brain imaging and spectroscopy and musculoskeletal imaging, but also body imaging, which is particularly challenging. Examples are given to demonstrate the advantages of susceptibility‐weighted imaging, time‐of‐flight MR angiography, high‐resolution functional MRI, 1H and 31P MRSI in the human brain, sodium and functional imaging of cartilage and the first results (and artefacts) using an eight‐channel body array, suggesting future areas of research that should be intensified in order to fully explore the potential of 7‐T MR systems for use in clinical diagnosis. Copyright

Quantification of aortic regurgitation by magnetic resonance velocity mapping

The use of magnetic resonance (MR) velocity mapping in the quantification of aortic valvular blood flow was examined in 10 patients with angiographically verified aortic regurgitation. MR velocity mapping succeeded in identifying and quantifying the regurgitation in all patients, and the regurgitant volume determined with MR velocity mapping agreed well with the grade obtained by aortic root angiography (p < 0.02). The accuracy in quantification of the aortic valvular flow rate was demonstrated by a significant correlation between the stroke volume (ml) measured by MR velocity mapping and calculated from MR imaging of the left ventricular end-diastolic and end-systolic volumes in eight patients (Y = 0.89 x X + 11, r = 0.97, p < 0.001). This finding was confirmed by a good agreement between the net cardiac output (L/min) quantified with MR velocity mapping and simultaneous 125I-indicator dilution measurement in all subjects (Y = 0.89 x X + 0.08, r = 0.82, p < 0.01). In conclusion, MR velocity mapping may be used as a noninvasive tool in the quantification of aortic regurgitation.

Perfusion-related parameters in intravoxel incoherent motion MR imaging compared with CBV and CBF measured by dynamic susceptibility-contrast MR technique

Objective: Perfusion-related parameters obtained by intravoxel incoherent motion (IVIM) MR imaging (MRI) were compared with cerebral blood volume and flow (CBV and CBF), retrieved by dynamic susceptibility-contrast (DSC) MRI. Material and Methods: Twenty-eight volunteers (average age 68.5 years) were investigated. Spin-echo echo-planar imaging with IVIM-encoding gradients was employed (36 different b values, 0-1200 s/mm2). The perfusion fraction and the pseudo-diffusion coefficient were calculated for regions in thalamus gray matter and frontal white matter, using asymptotic and full fitting. In DSC-MRI, a Gd-DTPA-BMA contrast-agent bolus was monitored using simultaneous-dual FLASH. Deconvolution of the measured tissue concentration-versus-time curve with an arterial input function from the carotid artery was applied, and maps of CBV and CBF were calculated. Results: The correlation between the perfusion fraction and CBV was r=0.56 (p<0.0000006) using asymptotic fitting, and r=0.35 (p<0.0004) when full fitting was applied. Average CBF was 41.5 ml/(min 100 g), to be compared with the IVIM-based value of 63.6 ml/(min 100 g), obtained from the median value of the pseudo-diffusion coefficient in combination with assumptions about capillary network structure. Conclusion: The IVIM concept provided results that agreed reasonably with conventional CBV and CBF. The non-linear fitting to noisy signal data was problematic, in accordance with previously presented simulations.

99mTc-Labeled Superparamagnetic Iron Oxide Nanoparticles for Multimodality SPECT/MRI of Sentinel Lymph Nodes

The purpose of this study was to develop multimodality SPECT/MRI contrast agents for sentinel lymph node (SLN) mapping in vivo. Methods: Nanoparticles with a solid iron oxide core and a polyethylene glycol coating were labeled with 99mTc. The labeling efficiency was determined with instant thin-layer chromatography and magnetic separation. The stability of the radiolabeled superparamagnetic iron oxide nanoparticles (SPIONs) was verified in both sterile water and human serum at room temperature 6 and 24 h after labeling. Five Wistar rats were injected subcutaneously in the right hind paw with 99mTc-SPIONs (25–50 MBq, ∼0.2 mg of Fe) and sacrificed 4 h after injection. Two animals were imaged with SPECT/MRI. All 5 rats were dissected; the lymph nodes, liver, kidneys, spleen, and hind paw containing the injection site were removed and weighed; and activity in the samples was measured. The microdistribution within the lymph nodes was studied with digital autoradiography. Results: The efficiency of labeling of the SPIONs was 99% 6 h after labeling in both water and human serum. The labeling yield was 98% in water and 97% in human serum 24 h after labeling. The SLN could be identified in vivo with SPECT/MRI. The accumulation of 99mTc-SPIONs (as the percentage injected dose/g [%ID/g]) in the SLN was 100 %ID/g, whereas in the liver and spleen it was less than 2 %ID/g. Digital autoradiography images revealed a nonhomogeneous distribution of 99mTc-SPIONs within the lymph nodes; nanoparticles were found in the cortical, subcapsular, and medullary sinuses. Conclusion: This study revealed the feasibility of labeling SPIONs with 99mTc. The accumulation of 99mTc-SPIONs in lymph nodes after subcutaneous injection in animals, verified by SPECT/MRI, is encouraging for applications in breast cancer and malignant melanoma.

Absolute quantification of perfusion using dynamic susceptibility contrast MRI: pitfalls and possibilities.

Absolute quantification of cerebral blood flow, cerebral blood volume and mean transit time is desirable in the determination of tissue viability thresholds and tissue at risk in acute ischaemic stroke, as well as in cases where a global reduction in cerebral blood flow is expected, for example, in patients with dementia or depressive disorders. Absolute values are also useful when comparing sequential examinations of tissue perfusion parameters, for example, in the monitoring and follow-up of various kinds of therapy. Regardless of the method employed, a number of assumptions and approximations must be made to obtain absolute measures of perfusion. Furthermore, the different stages of data acquisition and processing are associated with various degrees of uncertainty. In this review, the problems of particular relevance to absolute quantification of cerebral perfusion parameters using dynamic susceptibility contrast magnetic resonance imaging are discussed, and possible solutions are outlined.

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.

Is aqueductal stroke volume, measured with cine phase-contrast magnetic resonance imaging scans useful in predicting outcome of shunt surgery in suspected normal pressure hydrocephalus?

OBJECTIVETo evaluate clinical usefulness of cerebrospinal fluid stroke volume (SV) assessed in the cerebral aqueduct, via cine phase-contrast magnetic resonance imaging, for predicting outcome after shunt surgery in suspected normal pressure hydrocephalus. METHODSThirty-eight patients with suspected normal pressure hydrocephalus were included. SV was assessed using cine phase-contrast magnetic resonance imaging, and the results were kept blinded until postoperative follow-up after 7 ± 5.8 months (mean ± standard deviation). Selection to surgery was based on a positive lumbar infusion test or cerebrospinal fluid tap test, and outcome was evaluated with objective tests. RESULTSSix patients were excluded from SV measurements because of technical difficulties. Eight patients were not operated (negative lumbar infusion test and cerebrospinal fluid tap test). SV in the not operated patients (mean, 66 ± 53 μl) did not differ from the operated patients (95 ± 78 μl; P = 0.335). Operated patients showed statistically significant improvements in walk (P = 0.020), reaction time (P = 0.006), and memory (P = 0.001) tests. Patients were divided into three groups according to SV range: low (0–50 μl), middle (51–100 μl), and high (>100 μl). No statistically significant (P > 0.05) improvements in any of the objective tests were found in any of the SV ranges. The numbers of individually improved patients were similar in the different SV ranges: six out of seven in the low, nine out of nine in the middle, and five out of eight in the high range. Weak correlations were found between SV and the initial pulse amplitude (Rs = 0.043; P = 0.014) as well as the plateau pulse amplitude (Rs = 0.043; P = 0.014) as measured with the lumbar infusion test. CONCLUSIONThe data from this study show no evidence that cine phase-contrast magnetic resonance imaging measurements of SV in the cerebral aqueduct are useful for selecting patients with normal pressure hydrocephalus symptoms to shunt surgery.