Linda Knutsson

Increase in Hippocampal Volume After Electroconvulsive Therapy in Patients With Depression : A Volumetric Magnetic Resonance Imaging Study

Background: Major depression has traditionally been regarded as a neurochemical disease, but findings of a decreased hippocampal volume in patients with depression have turned the pathophysiological focus toward impairments in structural plasticity. The mechanisms of action of the most effective antidepressive treatment, electroconvulsive therapy (ECT), still remains elusive, but recent animal research has provided evidence for a cell proliferative effect in the hippocampus. The aim of this prospective study was to determine if hippocampal volume changes after ECT in patients with depression. Methods: Twelve patients with depression and ongoing antidepressive pharmacological treatment were investigated with clinical ratings and 3 T magnetic resonance imaging within 1 week before and after the ECT series. Each hippocampus was manually outlined on coronal slices, and the volume was calculated. Results: The left as well as the right hippocampal volume increased significantly after ECT. Conclusions: The hippocampal volume increases after ECT, supporting the hypothesis that hippocampus may play a central role in the treatment of depression.

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.

Diffusion and perfusion MRI of the brain in comatose patients treated with mild hypothermia after cardiac arrest: A prospective observational study.

BACKGROUND Outcome for resuscitated cardiac arrest (CA) patients is poor. The 1-year survival rate with favourable neurological outcome (CPC 1-2) after out-of-hospital CA is reported to be 4%. Among resuscitated patients treated within an ICU, approximately 50% regain consciousness, whereas the other 50% remain comatose before they die. Induced hypothermia significantly improves the neurological outcome and survival in patients with primary CA who remain comatose after return of spontaneous circulation. AIM To evaluate magnetic resonance imaging (MRI) changes in resuscitated CA patients remaining in coma after treatment with hypothermia. METHODS This prospective, observational study comprised 20 resuscitated CA patients who remained in coma 3 days after being treated with mild hypothermia (32-34 degrees C during 24h). Diffusion and perfusion MRI of the entire brain was performed approximately 5 days after CA. Autopsy was done on two patients. RESULTS The largest number of diffusion changes on MRI was found in the 16 patients who died. The parietal lobe showed the largest difference in number of acute ischaemic MRI lesions in deceased compared with surviving patients. Perfusion changes, > or = +/-2 SD compared with healthy volunteers from a previously published cerebral perfusion study, were found in seven out of eight patients. The autopsies showed lesions corresponding to the pathologic changes seen on MRI. CONCLUSION Diffusion and perfusion MRI are potentially helpful tools for the evaluation of ischaemic brain damage in resuscitated comatose patients treated with hypothermia after CA.

Absolute quantification of cerebral blood flow in normal volunteers: correlation between Xe-133 SPECT and dynamic susceptibility contrast MRI.

To compare absolute cerebral blood flow (CBF) estimates obtained by dynamic susceptibility contrast MRI (DSC‐MRI) and Xe‐133 SPECT.

Dynamic Glucose-Enhanced (DGE) MRI: Translation to Human Scanning and First Results in Glioma Patients

Recent animal studies have shown that d-glucose is a potential biodegradable magnetic resonance imaging (MRI) contrast agent for imaging glucose uptake in tumors. We show herein the first translation of that use of d-glucose to human studies. Chemical exchange saturation transfer (CEST) MRI at a single frequency offset optimized for detecting hydroxyl protons in d-glucose was used to image dynamic signal changes in the human brain at 7 T during and after d-glucose infusion. Dynamic glucose enhanced (DGE) image data from 4 normal volunteers and 3 glioma patients showed a strong signal enhancement in blood vessels, while a spatially varying enhancement was found in tumors. Areas of enhancement differed spatially between DGE and conventional gadolinium-enhanced imaging, suggesting complementary image information content for these 2 types of agents. In addition, different tumor areas enhanced with d-glucose at different times after infusion, suggesting a sensitivity to perfusion-related properties such as substrate delivery and blood-brain barrier (BBB) permeability. These preliminary results suggest that DGE MRI is feasible for studying glucose uptake in humans, providing a time-dependent set of data that contains information regarding arterial input function, tissue perfusion, glucose transport across the BBB and cell membrane, and glucose metabolism.

Absolute quantification of cerebral blood flow: correlation between dynamic susceptibility contrast MRI and model-free arterial spin labeling

PURPOSE To compare absolute cerebral blood flow (CBF) estimates obtained by model-free arterial spin labeling (ASL) and dynamic susceptibility contrast MRI (DSC-MRI), corrected for partial volume effects (PVEs). METHODS CBF was measured using DSC-MRI and model-free ASL (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) at 3 T in 15 subjects with brain tumor, and the two modalities were compared with regard to CBF estimates in normal gray matter (GM) and DSC-to-ASL CBF ratios in selected tumor regions. The DSC-MRI CBF maps were calculated using a global arterial input function (AIF) from the sylvian-fissure region, but, in order to minimize PVEs, the AIF time integral was rescaled by a venous output function time integral obtained from the sagittal sinus. RESULTS In GM, the average DSC-MRI CBF estimate was 150+/-45 ml/(min 100 g) (mean+/-SD) while the corresponding ASL CBF was 44+/-10 ml/(min 100 g). The linear correlation between GM CBF estimates obtained by DSC-MRI and ASL was r=.89, and observed DSC-to-ASL CBF ratios differed by less than 3% between GM and tumor regions. CONCLUSIONS A satisfactory positive linear correlation between the CBF estimates obtained by model-free ASL and DSC-MRI was observed, and DSC-to-ASL CBF ratios showed no obvious tissue dependence.

Calculation of cerebral perfusion parameters using regional arterial input functions identified by factor analysis

To calculate regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and regional mean transit time (rMTT) accurately, an arterial input function (AIF) is required. In this study we identified a number of AIFs using factor analysis of dynamic studies (FADS), and performed the cerebral perfusion calculation pixel by pixel using the AIF that was located geometrically closest to a certain voxel.

Dynamic glucose enhanced (DGE) MRI for combined imaging of blood-brain barrier break down and increased blood volume in brain cancer.

Recently, natural d‐glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d‐glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown.

Correlation between arterial blood volume obtained by arterial spin labelling and cerebral blood volume in intracranial tumours.

ObjectiveTo compare measurements of the arterial blood volume (aBV), a perfusion parameter calculated from arterial spin labelling (ASL), and cerebral blood volume (CBV), calculated from dynamic susceptibility contrast (DSC) MRI. In the clinic, CBV is used for grading of intracranial tumours.Materials and methodsEstimates of aBV from the model-free ASL technique quantitative STAR labelling of arterial regions (QUASAR) experiment and of DSC-CBV were obtained at 3T in ten patients with eleven tumours (three grade III gliomas, four glioblastomas and four meningiomas, two in one patient). Parametric values of aBV and CBV were determined in the tumour as well as in normal grey matter (GM), and tumour-to-GM aBV and CBV ratios were calculated.ResultsIn a 4-pixel ROI representing maximal tumour values, the coefficient of determination R2 was 0.61 for the comparison of ASL-based aBV tumour-to-GM ratios and DSC-MRI-based CBV tumour-to-GM ratios and 0.29 for the comparison of parametric values of ASL-aBV and DSC-CBV, under the assumption of proportionality. Both aBV and CBV showed a non-significant tendency to increase when going from grade III gliomas to glioblastomas to meningiomas.ConclusionThese results suggest that measurement of aBV is a potential tool for non-invasive assessment of blood volume in intracranial tumours.