Usefulness of functional MRI associated with PET scan and evoked potentials in the evaluation of brain functions after severe brain injury: preliminary results.

OBJECTIVE: To evaluate the feasability and the potential usefulness of functional MRI (fMRI) for the evaluation of brain functions after severe brain injury, when compared to a multimodal approach (evoked potentials [EP] and Positron Emission Tomography [PET] examinations). MATERIAL AND METHODS: Seven patients (mean age: 49 years [23-73], three males, four females) presenting with coma after acute severe brain injuries underwent fMRI (auditive, visual, somesthesic), (18)F-FDG PET and EP (auditive, visual, somesthesic) within a 3-day period of time in a mean of 120 days after initial brain injury. fMRI activations in somesthesic, visual and auditive cortical areas were compared to EP (28 possible comparisons) and to the metabolic activity on PET examination in the same anatomical areas (21 possible comparisons). RESULTS: In case of availability, results were concordant between fMRI and PET in 10 comparisons but not in one, and between fMRI and EP in 11 comparisons but not in four. CONCLUSIONS: In many patients, there is a good concordance between fMRI and brain functions suggested by EP and metabolic activity demonstrated with PET. In few others, fMRI can be integrated in the early evaluation of brain functions to further augment our capacity for a proper evaluation of brain functions in critically ill patients.

Effects of lorazepam on brain activity pattern during an anxiety symptom provocation challenge.

Human models of anxiety are useful to develop new effective anxiolytics. The objective of this study was to use functional magnetic resonance imaging (fMRI) to test the hypothesis that a single dose of lorazepam modifies brain activation during an anxiety challenge. Eighteen healthy male subjects underwent fMRI associated with a challenge based on the anticipation of aversive electrical stimulations after pretreatment, either with placebo or with 1.0 mg of oral lorazepam. Anxiety was rated before fMRI and after, referring to the threat condition periods, using State Trait Anxiety Inventory (STAI) and Hamilton scales. The conditioning procedure induced anxiety, as indicated by clinical rating score changes. Lorazepam did not modify anxiety rating as compared to placebo. Lorazepam reduced cerebral activity in superior frontal gyrus, anterior insula/inferior frontal gyrus and cingulate gyrus. The current finding provides the first evidence of the modulatory effects of an established anxiolytic agent on brain activation related to anticipatory anxiety.

Restless legs syndrome and low brain iron levels in patients with haemochromatosis.

Regional brain iron levels of two patients with haemochromatosis and severe restless legs syndrome (RLS) were assessed using R2' magnetic resonance imaging (MRI) sequences in both patients and in nine healthy controls. R2' relaxation rates in the patients were decreased in the substantia nigra, red nucleus, and pallidum when compared with the controls. These results indicate that local brain iron deficiency may occur in patients with haemochromatosis and suggest a role for brain iron metabolism in the pathophysiology of RLS.

Oxygen consumption through metabolism and photodynamic reactions in cells cultured on microbeads.

Oxygen consumption by cultured cells, through metabolism and photosensitization reactions, has been calculated theoretically. From this result, we have derived the partial oxygen pressure PO2 in the perfusion medium flowing across sensitized cultured cells during photodynamic experiments. The PO2 variations in the perfusate during light irradiation are related to the rate of oxygen consumption through photoreactions, and to the number of cells killed per mole of oxygen consumed through metabolic processes. After irradiation, the reduced metabolic oxygen consumption yields information on the cell death rate, and on the photodynamic cell killing efficiency. The aim of this paper is to present an experimental set-up and the corresponding theoretical model that allows us to control the photodynamic efficiency for a given cell-sensitizer pair, under well defined and controlled conditions of irradiation and oxygen supply. To demonstrate the usefulness of the methodology described, CHO cells cultured on microbeads were sensitized with pheophorbide a and irradiated with different light fluence rates. The results obtained, i.e. oxygen consumption of about 0.1 microM s(-1) m(-3) under a light fluence rate of 1 W m(-2), 10(5) cells killed per mole of oxygen consumed and a decay rate of about 1 h(-1) of living cells after irradiation, are in good agreement with the theoretical predictions and with previously published data.

Experimental observation of photochemically induced oxygen depletion in perfused cells undergoing photodynamic therapy.

This report presents a non invasive method for studying oxygen consumption during photodynamic therapy in cultured cells. The oxygen partial pressure of perfusion medium flowing through cells cultured on microcarrier beads, was investigated before, during and after treatment. Pheophorbide a was used as a sensitiser. Time-dependent measurements demonstrate photochemical oxygen depletion induced by photosensitized reactions, followed by an oxygen pressure increase were attributed to a reduction in the cells' metabolism.

31P NMR spectroscopy of photodynamically treated cells.

The metabolic response of Chinese Hamster Ovary (CHO) cells during photodynamic therapy (PDT) with hematoporphyrin IX (Hp IX) and pheophorbide (Ph) was monitored in real time by 31-phosphorous (31P) nuclear magnetic resonance (NMR) spectroscopy. The effects of the delivered light dose and of cell oxygenation were investigated. A delayed disappearance of nucleoside triphosphate (NTP) following irradiation was observed, which was related to the treatment efficiency. For cells irradiated with a light dose of 0.8 J/cm2 in the presence of Hp IX, the disappearance of the NTP peaks occurred within 30 minutes of irradiation, but for an irradiation of 0.24 J/cm2, the disappearance of the NTP peaks occurred about 6 hours later, and this delayed disappearance is related to the surviving fraction. For irradiation experiments involving Ph and a light dose of 0.036 J/cm2, NTP in injured cells began to decrease about 3 hours after irradiation, whereas for a light dose of 0.24 J/cm2, we observed the instantaneous disappearance of the NTP peaks occurring during the irradiation time. The same efficiency was obtained with two different oxygen partial pressures in the perfusate (360 and 154 mmHg) and a light dose of 0.24 J/cm2.

Diagnosis of prospective malignancy in koilocytic dysplasias of the cervix with DNA cytometry.

DNA cytometric measurements were performed with a TV image analysis system on 90 routine cytologic cervical smears from 18 women after automatic restaining of the smears with the Feulgen method. In the cytologic follow-up all the patients revealed borderline lesions (mild to moderate dysplasia) of the epithelium with koilocytosis. Since DNA aneuploidy is widely accepted as a marker for malignancy, an attempt was made to obtain a DNA diagnosis of prospective malignancy in these cases on the basis of the detection of single aneuploid cells. Because koilocytosis strongly suggests human papillomavirus infection, euploid polyploidy might result in up to 8c (c = haploid amount of DNA). Therefore, the aneuploidy detection threshold was set to 9c, excluding values around 16c and 32c (+/- 12.5%) to avoid false-positive diagnoses in cases of higher polyploidy values. The DNA diagnosis of malignancy was made in 13 patients. In 12 of them, carcinoma in situ was diagnosed in the histologic follow-up, resulting in 100% sensitivity of the DNA diagnosis. In five patients no cells greater than 9c were measured, leading to a benign DNA diagnosis. In the histologic follow-up, six patients revealed normal epithelium or moderate dysplasia. Thus, the specificity of the DNA diagnosis was 83.3%.