Quantification of cerebral perfusion with "Real-Time" contrast-enhanced ultrasound.

BACKGROUND: No noninvasive technique is currently capable of "real-time" assessment and monitoring of cerebral blood flow (CBF). We hypothesized that cerebral perfusion could be accurately measured and monitored in "real time" with contrast-enhanced ultrasound (CEU). METHODS AND RESULTS: Cerebral perfusion was assessed in 9 dogs through a craniotomy with CEU at baseline and during hypercapnia and hypocapnia while normoxia was maintained. Cerebral microvascular blood volume (A), microbubble velocity (beta), and blood flow (Axbeta) were calculated from time-versus-acoustic intensity relations. Compared with baseline, hypercapnia and hypocapnia significantly increased and decreased CBF, respectively, as measured by CEU. These changes in blood flow were mediated by changes in both A and beta. A good correlation was found between Axbeta derived from CEU and CBF measured by radiolabeled microspheres (y=0.67x-0.04, r=0.91, P<0.001). CONCLUSIONS: Changes in both cerebral microvascular blood volume and red blood cell velocity can be accurately assessed with CEU. Thus, CEU has the potential for bedside measurement and monitoring of cerebral perfusion in real time in patients with craniotomies or burr holes.

MR imaging and spectroscopy using hyperpolarized 129Xe gas: preliminary human results.

Using a new method of xenon laser-polarization that permits the generation of liter quantities of hyperpolarized 129Xe gas, the first 129Xe imaging results from the human chest and the first 129Xe spectroscopy results from the human chest and head have been obtained. With polarization levels of approximately 2%, cross-sectional images of the lung gas-spaces with a voxel volume of 0.9 cm3 (signal-to-noise ratio (SNR), 28) were acquired and three dissolved-phase resonances in spectra from the chest were detected. In spectra from the head, one prominent dissolved-phase resonance, presumably from brain parenchyma, was detected. With anticipated improvements in the 129Xe polarization system, pulse sequences, RF coils, and breathing maneuvers, these results suggest the possibility for 129Xe gas-phase imaging of the lungs with a resolution approaching that of current conventional thoracic proton imaging. Moreover, the results suggest the feasibility of dissolved-phase imaging of both the chest and brain with a resolution similar to that obtained with the gas-phase images.

Patient characteristics and pre-operative therapeutic modalities.

The International Cooperative Study on the Timing of Aneurysm Surgery included 68 participating centers from 16 different countries. Eight Italian neurosurgical units participated in the Study: Bellaria Hospital, Bologna; Neurological Institute of Milan, Milan; University Hospital, Brescia; University of Milan, Milan; University of Padova, Padova; University of Rome, Rome; Civil Hospital, Verona; and Civil Hospital, Vicenza. The overall case contribution from the Italian centers was 485 cases, 14.1% of the total study population. As compared to the other centers included in the Study, the Italian centers exhibited a higher percentage of patients with impaired consciousness; a later interval of planned surgery from SAH; frequent use of preoperative lumbar drainage, as well as antihypertensives, anticonvulsants, antifibrinolytics, steroids, diuretics and LMW dextran; and less frequent use of sedatives and narcotics. The individual Italian centers differed significantly in regard to patient characteristics and preoperative therapeutic modalities. There was a relatively high number of stuporous or comatose patients admitted to Centers 1, 7 and 8, very few admitted to Centers 5 and 6, and none admitted to Center 2. The different distribution of key prognostic factors prevents a direct comparison of the overall management results of the centers. A stratification of the patients according to a risk scale and/or a prognostic model is required for comparison of the management results.

Surgical findings and postoperative therapeutic modalities.

The 8 Italian centers participating in the International Cooperative Study on Timing of Aneurysm Surgery operated upon 68% of their patients eligible for the study. This low operative rate is mainly explained by the prevailing use of a delayed surgical policy. Only 28% of cases were operated on within 3 days of hemorrhage. Although early surgery was applied in more than 50% of patients from Centers 2, 6 and 7, most other centers operated on approximately 10% of patients within this time interval. Italian centers exhibited a wide variation in planned and actual surgery interval, with only 48% of their patients eventually operated on at the planned time. Differences from planned and actual timing of surgery were less consistent in the units performing early surgery. Preoperative conditions were different between the individual centers. The percent of patients alert at the time of surgery varied from approximately 50% in Centers 3 and 7 to 90% in Center 5. Centers 2 and 6 never operated on comatose patients and rarely stuporous patients. During surgery, induced hypotension was used in 67% of Italian patients. The brain was tight at exposure in 42% of patients from Italian centers; the difference from the other study centers was very significant (p = 0.0009). Consequently major brain resection was more frequently performed in Italy than in the other centers. Brain conditions depended mainly upon timing of surgery and preoperative grade (except for comatose patients) and varied accordingly between the individual centers. Temporary arterial occlusion was rarely used in Italian centers. Intraoperative bleeding from the aneurysm was slightly more frequent than in the other centers. The overall incidence of intraoperative complications was unremarkable. There were significant differences between the Italian and the other centers regarding the use of postoperative routines and medications. In Italian centers ventricular CSF drainage, shunt insertion, ICP monitoring, sedatives and analgesics were less frequently used; lumbar CSF drainage, anticonvulsants, steroids, and diuretics were applied more frequently. In the individual centers the major differences were in the use of antihypertensives, vasopressor agents, diuretics, hypervolemia, and low-molecular weight dextran.

Results of treatment.

Overall results of management in patients admitted to the 8 Italian centers participating in the International Cooperative Study on Timing of Aneurysm Surgery were rather unsatisfactory, with good recovery in only 42% of patients, and death in 45% of patients. As compared to the other centers included in the Study, Italian centers exhibited a significantly lower recovery rate and a significantly higher mortality rate. There were significant differences also between the individual Italian centers; independently of admission neurological status and timing of surgery, the outcome was better in centers 2 and 6 (a mortality rate under 20%) and worse in centers 1 and 8 (a mortality rate around 60%). Using prognostic factor models, higher than expected mortality rates were observed in 4 centers, and lower than expected good recovery rates in 3 centers. In Italian centers vasospasm accounted for the highest morbidity and mortality rate; the difference in mortality rate from vasospasm between Italian and other centers was very significant. Other important causes of death and disability were constituted by direct effect of the initial bleed and by recurrent hemorrhage. Patients operated on in Italian centers exhibited a good recovery in 57% of cases; the mortality was 27%. Differences from the other centers were less marked than for the overall management results. Mortality rates from vasospasm and from surgical complications were significantly higher in Italian than in the other study centers. Between the individual Italian centers, vasospasm accounted for the highest mortality rate in centers 7 and 8 (17% and 28% respectively). Postoperative pneumonia was significantly more frequent in Italian than in the other centers. In regard to timing of surgery, the differences in results between Italian and other centers were less marked when surgery was performed after 10 days from hemorrhage. In Italian centers as a whole, a delayed operation was linked with a better outcome than an early or subacute operation. The lowest recovery rate was observed in drowsy patients operated on between 4 and 10 days from the hemorrhage. Focal ischemic deficits and pneumonia were prevalent after an operation within 3 days of hemorrhage, while postoperative brain swelling was most frequent in patients operated on between 4 and 10 days from hemorrhage. The differences in results between Italian and other centers and among the individual Italian centers are widely discussed; possible explanations include inadequate modalities of treatment (especially inadequate management of vasospasm) and structural deficiencies of intensive care management in seriously ill patients.