Squeezed-Light Enhancement and Backaction Evasion in a High Sensitivity Optically Pumped Magnetometer.

We study the effect of optical polarization squeezing on the performance of a sensitive, quantum-noise-limited optically pumped magnetometer. We use Bell-Bloom (BB) optical pumping to excite a ^{87}Rb vapor containing 8.2×10^{12} atoms/cm^{3} and Faraday rotation to detect spin precession. The sub-pT/sqrt[Hz] sensitivity is limited by spin projection noise (photon shot noise) at low (high) frequencies. Probe polarization squeezing both improves high-frequency sensitivity and increases measurement bandwidth, with no loss of sensitivity at any frequency, a direct demonstration of the evasion of measurement backaction noise. We provide a model for the quantum noise dynamics of the BB magnetometer, including spin projection noise, probe polarization noise, and measurement backaction effects. The theory shows how polarization squeezing reduces optical noise, while measurement backaction due to the accompanying ellipticity antisqueezing is shunted into the unmeasured spin component. The method is compatible with high-density and multipass techniques that reach extreme sensitivity.

Different roles of matrix metalloproteinases-2 and -9 after human ischaemic stroke.

Accumulating data suggest that matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9, are deleterious after acute ischaemic stroke. A beneficial effect of MMPs in the repairing phases of cerebral ischaemia has also been proposed. This study investigated the relationship between MMP-2 and MMP-9 and stroke subtypes, clinical recovery and haemorrhagic transformation (HT). We measured MMP-9 and MMP-2 plasma levels in 29 patients with ischaemic stroke at days one and seven. MMP-2 levels increased only in lacunar strokes, whilst MMP-9 increased only in patients with more severe stroke. Basal MMP-2 levels were higher in patients with stable or recovering symptoms whilst MMP-9 values at day seven were correlated with worse clinical outcome. No differences related to the presence of HT were found. This study sustains a different behaviour of MMPs after ischaemic stroke. MMP-2 seems to be expressed early and related to better outcome, whilst MMP-9 seems to be late and related to more severe stroke.

Multimodal MR examination in acute ischemic stroke.

In recent years, combined diffusion-weighted imaging (DWI) with perfusion imaging (PI) has become an important investigational tool in the acute phase of ischemic stroke, as it may differentiate reversible from irreversible brain tissue damage. We consecutively examined 20 subjects within 12 h of stroke onset using a multiparametric magnetic resonance (MR) examination consisting of DWI, mean transit time (MTT) as PI parameter, and MR angiography (MRA). T2-weighted and fluid-attenuated inversion recovery (FLAIR) on day 7 were also acquired in order to obtain final infarct volume. The following MR parameters were considered: volumetric measures of lesion growth and MTT abnormalities, quantification of regional apparent diffusion coefficient (ADC) and visual inspection of MRA findings. Our results showed: (1) an acute DWI lesion was not predictive of lesion growth and the DWI abnormality did not represent the irreversibly infarcted tissue; (2) ADC values in the ischemic penumbra could not predict tissue at risk; (3) the DWI-PI mismatch did not predict lesion growth, and the PI abnormality overestimated the amount of tissue at risk; and (4) patients with proximal middle cerebral artery occlusion had greater initial and final infarct volumes. This study did not demonstrate the prognostic value of a multimodal MR approach in early ischemic stroke; MRA alone provided predictive information about the volumetric evolution of the lesion.

Ischaemic stroke in progressive systemic sclerosis.

Progressive systemic sclerosis (PSS) or scleroderma is a multisystem disease affecting the skin, lungs, myocardium, kidneys and gastrointestinal tract. Primary involvement of cerebral arteries in PSS has been reported but is very rare. A 61-year-old woman suffering from scleroderma for six years was hospitalised for two subsequent episodes of transient acute dysarthria and left hemiparesis. After five hours from the first onset of symptoms, she was submitted to brain magnetic resonance (MR) protocol that showed a right subinsular ischaemic lesion and whole right middle cerebral artery (MCA) territory hypoperfusion. Intracranial and epiaortic MR angiography reported a focal stenosis in the M2 portion of MCA. She was immediately treated with i.v. high dose steroids and oral acetylsalicylic acid. At one-month follow up, MR findings were confirmed. We have documented a cerebral infarct in a PSS patient. In our opinion, the ischaemic stroke was caused by a localised autoimmune angiopathy.

Proton MR spectroscopy in idiopathic spasmodic torticollis.

Single-voxel proton magnetic resonance spectroscopy (1H-MRS), localised to the basal ganglia, was used to determine changes in metabolite levels in idiopathic spasmodic torticollis (IST). We examined nine patients and 13 healthy subjects. The mean values (+/- SD) of peak area ratios were: IST: N-acetyl-aspartate (NAA)/choline-containing compounds (Cho) 1.79 +/- 0.39, NAA/creatine and phosphocreatine compounds (Cr) 1.61 +/- 0.38, Cho/Cr 0.91 +/- 0.19; controls: NAA/Cho 2.07 +/- 0.35, NAA/ Cr 1.82 +/- 0.31, Cho/Cr 0.89 +/- 0.12. Statistical analysis showed that NAA/Cho and NAA/Cr were significantly lower in patients than in controls (P = 0.0304 and 0.0431, respectively). These results indicate a reduction in NAA, and suggest striatal involvement in the pathogenesis IST.

Axonal damage in multiple sclerosis plaques: a combined magnetic resonance imaging and 1H-magnetic resonance spectroscopy study.

The purpose of this study was to compare magnetic resonance imaging (MRI) features and proton MR spectroscopy (1H-MRS) patterns of multiple sclerosis (MS) plaques in order to define the metabolic substrate in different lesion subtypes. Combined MRI and single-voxel 1H-MRS investigation was performed in 54 MS patients (47 relapsing remitting (RR) and seven secondary progressive (SP)). Sixty-seven MS lesions were selected. Thirty-seven lesions were Gadolinium (Gd) enhancing (nine isointense and 28 hypointense on pre-contrast T(1)-weighted scans) and 30 Gd unenhancing (six isointense and 24 hypointense on pre- and post-contrast T(1)-weighted scans). Choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate were evaluated in 1H spectra acquired from MS plaques and from normal white matter (NWM) of 22 neurological controls. MS lesions of RR patients were characterized by a significant increase of Cho/Cr and decrease of NAA/Cr and NAA/Cho ratios. No significant metabolite changes were found in lesions of SP patients. Gd enhancing plaques showed lactate signal with higher frequency (37.8%) than Gd unenhancing plaques (16.7%) (p=0.04). A significant increase of Cho/Cr was found in Gd enhancing lesions when compared to controls (p<0.01), and to Gd unenhancing lesions (p<0.05). In particular, there was evidence of a significant increase of Cho/Cr in pre-contrast T(1) hypointense Gd enhancing lesions (p<0.01 vs. controls). The Gd unenhancing lesions (p<0.01), in particular the T(1) hypointense group (p<0.05), showed a significant decrease of NAA/Cr only when compared to controls. These data confirm that in vivo MRS indicates key pathological features of MS plaques. The increased Cho/Cr ratio found in Gd-enhancing plaques, in particular in the T(1) hypointense lesions, may reflect increased membrane cell turnover. The T(1) hypointense Gd unenhancing plaques better reflect axonal damage, as suggested by the decrease of NAA/Cr. Nevertheless, the lack of statistical differences in NAA/Cr between plaque subgroups suggests that axonal impairment might occur even in the early stages.

Usefulness of proton magnetic resonance spectroscopy in differentiating parkinsonian syndromes.

Proton magnetic resonance spectroscopy ((1)H-MRS) was performed in patients with a clinical diagnosis of idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA) or progressive supranuclear palsy (PSP) in order to assess metabolic differences between the three groups of patients. Single-volume (1)H-MRS, localized to the lentiform nucleus, was carried out in 19 IPD patients, 14 MSA patients, 11 PSP patients and 12 age-matched healthy subjects. The signals of N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine-phosphocreatine (Cr) were evaluated as peak area ratios. The NAA/Cho peak ratio was significantly reduced in MSA and in PSP patients compared to IPD patients and to controls. The NAA/Cr peak ratio was significantly reduced in MSA, in PSP and in IPD patients compared to controls, but only in MSA compared to IPD patients. The NAA reduction in the basal ganglia of MSA and PSP patients may reflect a neuronal loss or damage. Single-volume (1)H-MRS may be a useful tool in differentiating MSA and PSP from IPD patients.

Metabolic changes in neuronal migration disorders: evaluation by combined MRI and proton MR spectroscopy.

PURPOSE: To assess the role of 1H-magnetic resonance spectroscopy (MRS) in detecting biochemical abnormalities in neuronal migration disorders (NMDs). METHODS: We performed 1H-MRS studies on 17 brain NMD areas [five polymicrogyria, eight subcortical heterotopia, and four cortical dysplasia on magnetic resonance imaging (MRI)]. The study group consisted of 15 patients, all but one affected by partial epileptic seizures. Spectra were acquired from volumes of interest localized on NMDs and contralateral sides and compared with those obtained on gray and white matter of 18 neurologic controls. RESULTS: NMD lesions were characterized by lower N-acetylaspartate to creatine (NAA/Cr) and choline to Cr (Cho/Cr) ratios than those of the white (p = 0.002 and p = 0.004) and gray matter (p = 0.03 and p = 0.06) of neurologic controls. In addition, the normal-appearing contralateral sides to the NMD lesions showed a significant decrease of Cho/Cr ratio when compared with those of white (p = 0.003) and gray matter (p = 0.05) of neurologic controls. No relation was found between NAA/Cr decrease, EEG abnormalities, and NMD sides, or between NAA/Cr ratios, duration of epilepsy, and frequency of seizures. Lactate signal was detected in the spectra of four patients who had an epileptic seizure a short time before MR examination. CONCLUSIONS: NAA/Cr decrease may be related more to structural and functional alteration of the NMD sides than to epileptic activity in these lesions. Low Cho/Cr may be related to a more extensive diffuse hypomyelination than suggested by the MRI findings. An activation of anerobic glycolysis during and after seizures could account for the presence of lactate. These data confirm that H-MRS is an advanced technique that may provide useful biochemical information in vivo on neurobiologic processes underlying NMDs.

Proton magnetic resonance spectroscopy in primary blepharospasm.

Single-volume proton magnetic resonance spectroscopy, localized to basal ganglia, was carried out in 10 patients with primary blepharospasm (PB) to assess the levels of N-acetyl aspartate (NAA), creatine-phosphocreatine, and choline-containing compounds. NAA was reduced significantly in patients compared with control subjects. This result suggests a striatal neuronal loss in PB.

Localised 1H-MR spectroscopy for metabolic characterisation of diffuse and focal brain lesions in patients infected with HIV.

OBJECTIVES: To evaluate the role of proton MR spectroscopy (1H-MRS) in detecting metabolic changes in diffuse or focal lesions in the brain of patients infected with HIV. METHODS: Sixty HIV seropositive patients (25 with HIV related encephalopathies, 20 with toxoplasmosis, eight with progressive multifocal leukoencephalopathies (PMLs), and seven with lymphomas) and 22 HIV seronegative neurological controls were examined with a combined MRI and 1H-MRS technique using a Siemens 1.5 Tesla Magnetom. Spectra (Spin Echo sequence, TE 135 ms) were acquired by single voxel, localised on focal lesions in toxoplasmosis, PML, lymphomas, and HIV encephalopathies and on the centrum semiovale of neurological controls. Choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), lactate, and lipids were evaluated in each spectrum and NAA/Cr, NAA/Cho, and Cho/Cr ratios were calculated. RESULTS: A significant decrease in NAA/Cr and NAA/Cho ratios were found in all HIV diagnostic groups in comparison with neurological controls (p<0.003), suggesting neuronal or axonal damage independent of brain lesion aetiology. However, the NAA/Cr ratio was significantly lower in PML and lymphomas than in HIV encephalopathies (p<0.02) and toxoplasmosis (p<0.05). HIV encephalopathies, lymphomas, and toxoplasmosis showed a significant increase in the Cho/Cr ratio in comparison with neurological controls (p<0.03) without between group differences. The presence of a lipid signal was more frequent in lymphomas (71%) than in other HIV groups (Fisher's test, p=0.00003). The presence of mobile lipid resonance together with a high Cho/Cr ratio in lymphomas may be related to an increased membrane synthesis and turnover in tumour cells. A lactate signal (marker of inflammatory reaction), was found in all but one patient with PML lesions (75%), but had a lower incidence in the other HIV diagnostic groups (Fisher's test, p=0.00024). CONCLUSION: 1H-MRS shows a high sensitivity in detecting brain involvement in HIV related diseases, but a poor specificity in differential diagnosis of HIV brain lesions. Nevertheless, the homogeneous metabolic pattern that characterises PML suggests the usefulness of 1H-MRS as an adjunct to MRI in differentiating CNS white matter lesions, such as HIV encephalopathies, from PML.

Prognostic value of proton magnetic resonance spectroscopy in ischemic stroke.

OBJECTIVE: To determine the correlation between metabolite concentrations and clinical outcome during the acute or subacute phase of ischemic stroke by using single-voxel localized proton magnetic resonance spectroscopy (1H-MRS). SETTING: A university hospital neurologic department. PATIENTS AND METHODS: Combined single-voxel 1H-MRS and magnetic resonance imaging were performed on 26 patients with a recent ischemic stroke (on 8 patients during the first 24 hours after the stroke and on 18 during the first week). For all patients, the signals from N-acetylaspartate, choline-containing compounds, and creatine-phosphocreatine were compared with those on the contralateral side as peak area ratios. The data for 1H-MRS were related to scores on the Scandinavian Stroke Scale and the Barthel Index at a 6-month clinical follow-up. RESULTS: The signals from N-acetylaspartate, choline-containing compounds, and creatine-phosphocreatine were significantly reduced in all infarcted areas (P<.001, P<.001, and P=.003, respectively, Wilcoxon signed rank test). A lactate signal was present in 19 patients. The statistical analysis showed a significant positive correlation between N-acetylaspartate signals and Scandinavian Stroke Scale scores and between reduction of N-acetylaspartate signals and Barthel Index scores (Spearman rank correlation test). Patients in whom lactate was present had Scandinavian Stroke Scale scores significantly lower than patients in the group without lactate (Mann-Whitney U test). CONCLUSION: Single-voxel 1H-MRS performed during the acute or subacute phase of ischemic stroke may provide prognostic information.

Proton magnetic resonance spectroscopy in Parkinson's disease and atypical parkinsonian disorders.

Proton magnetic resonance spectroscopy (1H-MRS), localized to the lentiform nucleus, was carried out in 12 patients with idiopathic Parkinson's disease (IPD), seven patients with multiple-system atrophy (MSA), seven patients with progressive supranuclear palsy (PSP), and 10 healthy age-matched controls. The study assessed the level of N-acetylaspartate (NAA), creatine-phosphocreatine (Cr), and choline (Cho) in the putamen and globus pallidus of these patients. NAA/Cho and NAA/Cr ratios were significantly reduced in MSA and PSP patients. No significant difference was found between IPD patients and controls. These results suggest an NAA deficit, due to neuronal loss, in the lentiform nucleus of MSA and PSP patients. 1H-MRS is a noninvasive technique that can provide useful information regarding striatal neuronal loss in basal ganglia of patients with atypical parkinsonian disorders and represents a potential tool for diagnosing these disorders.

Proton magnetic resonance spectroscopy in Parkinson's disease and progressive supranuclear palsy.

OBJECTIVES: Proton magnetic resonance spectroscopy (1H-MRS) localised to the lentiform nucleus, was carried out in eight patients with idiopathic Parkinson's disease and five patients with progressive supranuclear palsy. The aim of the study was to assess the concentration of N-acetyl-aspartate (NAA), creatine and phosphocreatine (Cr), and choline containing compounds (Cho) in the putamen and globus pallidus of these patients. METHODS: Peak ratios obtained from patients were compared with those from nine healthy age matched controls. RESULTS: NAA/Cho and NAA/Cr ratios were reduced significantly in patients with progressive supranuclear palsy. CONCLUSION: These results suggest an NAA deficit, due to neuronal loss, in the lentiform nucleus of these patients. 1H-MRS is a non-invasive technique that can provide useful information concerning striatal neuronal loss in the basal ganglia of patients with parkinsonian syndromes.

Prognostic significance of metabolic changes detected by proton magnetic resonance spectroscopy in ischaemic stroke.

Proton magnetic resonance spectroscopy has proved to be useful for monitoring a number of metabolites in cerebral infarction. Combined magnetic resonance imaging and spectroscopy investigations were carried out in 14 patients with a recent ischaemic stroke (< 1 week); follow-up examinations were performed from day 28 to day 252 after stroke. The aim of this study was to assess the correlation between the changes of N-acetyl-aspartate, choline, creatine-phosphocreatine, lactate and clinical evolution measured by the Scandinavian Neurological Scale (SNS). Initially the lactate magnetic resonance signal was present in all patients and the other metabolite contents were significantly reduced (P < 0.001; unpaired t-test) as compared with those on the contralateral side. Spearman's rank correlation test showed a positive correlation between the initial reduction of N-acetyl-aspartate content and the SNS (P < 0.05), and between the final N-acetyl-aspartate content and the SNS (P < 0.001). Our results suggest that serial examination in stroke patients may provide further prognostic information and encourage controlled clinical studies.

A double blind randomized pilot trial of naloxone in the treatment of acute ischemic stroke.

Attention has focused on naloxone, an opiate receptor antagonist, because of its potential benefit in reversing neurological damage after acute cerebral ischemia. To evaluate the safety and possible efficacy of high-dose naloxone in ischemic stroke patients we planned a double blind pilot study. Between January 1989 and May 1990 24 patients were randomly assigned to the naloxone or placebo group according to age and neurological deficit. Naloxone was given in a loading dose of 5 mg/kg over 10 minutes followed by a 24-hour infusion at the rate of 3.5 mg/kg/h. 10 patients experienced minor side effects but none of them had to discontinue the treatment. 9 patients improved: 6 in the naloxone group and 3 in the placebo group, but no significant difference was found using the non parametric Mann-Whitney test. Our study suggests that naloxone is safe at the dose used, but the results do not support the planning of similar trials on a larger scale.