First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas.

BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of copanlisib, a phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Phase I dose-escalation study including patients with advanced solid tumors or NHL, and a cohort of patients with type 2 diabetes mellitus. Patients received three weekly intravenous infusions of copanlisib per 28-day cycle over the dose range 0.1-1.2 mg/kg. Plasma copanlisib levels were analyzed for pharmacokinetics. Biomarker analysis included PIK3CA, KRAS, BRAF, and PTEN mutational status and PTEN immunohistochemistry. Whole-body [(18)F]-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) was carried out at baseline and following the first dose to assess early pharmacodynamic effects. Plasma glucose and insulin levels were evaluated serially. RESULTS: Fifty-seven patients received treatment. The MTD was 0.8 mg/kg copanlisib. The most frequent treatment-related adverse events were nausea and transient hyperglycemia. Copanlisib exposure was dose-proportional with no accumulation; peak exposure positively correlated with transient hyperglycemia post-infusion. Sixteen of 20 patients treated at the MTD had reduced (18)FDG-PET uptake; 7 (33%) had a reduction >25%. One patient achieved a complete response (CR; endometrial carcinoma exhibiting both PIK3CA and PTEN mutations and complete PTEN loss) and two had a partial response (PR; both metastatic breast cancer). Among the nine NHL patients, all six with follicular lymphoma (FL) responded (one CR and five PRs) and one patient with diffuse large B-cell lymphoma had a PR by investigator assessment; two patients with FL who achieved CR (per post hoc independent radiologic review) were on treatment >3 years. CONCLUSION: Copanlisib, dosed intermittently on days 1, 8, and 15 of a 28-day cycle, was well tolerated and the MTD was determined to be 0.8 mg/kg. Copanlisib exhibited dose-proportional pharmacokinetics and promising anti-tumor activity, particularly in patients with NHL. CLINICALTRIALSGOV: NCT00962611; https://clinicaltrials.gov/ct2/show/NCT00962611.

A noninvasive reporter system to image adenoviral-mediated gene transfer to ovarian cancer xenografts.

OBJECTIVE: Gene therapy trials for ovarian cancer would benefit from a noninvasive imaging modality to detect the location and extent of gene transfer. The human type 2 somatostatin receptor gene (hSSTr2) was evaluated as a reporter gene for imaging adenoviral (Ad) gene transfer to ovarian cancer. METHODS: A replication-incompetent Ad vector encoding hSSTr2 (Ad-hSSTr2) was used to infect SKOV3.ip1 cells in vitro and tumors growing in nude mice. Gamma camera imaging detected uptake of 99m-Tc-P2045 (a somatostatin analogue) due to expressed hSSTr2. RESULTS: Specific uptake of 99m-Tc-P2045 was imaged in Ad-hSSTr2-infected cells in vitro. Noninvasive in vivo imaging detected gene transfer to intraperitoneal tumors. Uptake of 99m-Tc-P2045 (percentage dose per gram of tumor) averaged 2.2 and 0.18 for Ad-hSSTr2-injected mice and controls, respectively. CONCLUSION: This study reports the first noninvasive imaging method for imaging gene transfer to ovarian cancer. A human gene therapy trial is planned.

Effect of dietary intake before F-18 FDG positron emission tomographic scanning on the evaluation of a solitary pulmonary nodule.

The uptake of fluorine-18 fluorodeoxyglucose (F-18 FDG) by a malignant tumor depends on the blood glucose level. The authors present a striking case that illustrates the importance of blood glucose measurement in F-18 FDG positron emission tomographic (PET) imaging in a patient with a solitary pulmonary nodule. With the emergence of freestanding imaging centers, this case emphasizes the importance of using an objective method, such as a glucometer, to measure blood glucose levels before F-18 FDG PET imaging. Results of the initial scan were equivocal (the patient had eaten before the scan), whereas a hypermetabolic focus was clearly identified on a second scan obtained 2 days later.

Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles.

The present study analyzed the feasibility of using magnetic resonance imaging (MRI) to monitor T-cell homing in vivo after loading T cells with superparamagnetic iron oxide (CLIO) nanoparticles derivatized with a peptide sequence from the transactivator protein (Tat) of HIV-1. T cells were isolated from C57BL/6 (B6) mice and loaded with 0, 400, 800, 1600, or 8000 ng/ml of FITC conjugated CLIO-Tat (FITC-CLIO-Tat). There was a dose-dependent uptake of FITC-CLIO-Tat by T cells. Stimulation of FITC-CLIO-Tat loaded T cells with anti-CD3 (0.1 microg/ml) plus IL-2 (5 ng/ml) elicited normal activation and activation-induced cell death (AICD) responses, and normal upregulation of CD69, ICAM-1 (CD54), L-selectin (CD62L), and Fas. The FITC-CLIO-Tat loaded T cells (3 x 10(7)) were transferred intravenously (i.v.) into B6 mice and the in vivo MRI of mice was acquired using a spin-echo pulse sequence at 4.7 T with a Bruker Biospec system. Homing of T cells into the spleen was observed by a decrease in MRI signal intensity within 1 h after the transfer, which remained decreased for 2-24 h after transfer. These homing data were confirmed by FACS analysis and biodistribution analysis using 125I-CLIO-Tat. Thus, T cells can be efficiently loaded with FITC-CLIO-Tat without interfering with their normal activation and AICD, or homing to the spleen, and the biodistribution of FITC-CLIO-Tat loaded T cells can be monitored in vivo over time by MRI.

Light-based imaging of green fluorescent protein-positive ovarian cancer xenografts during therapy.

OBJECTIVE: The purpose of the study was to develop a sensitive, noninvasive imaging method for monitoring ovarian xenografts during therapeutic intervention. METHODS: Human ovarian tumor cells (SKOV3.ip1) were infected with a replication-deficient adenoviral (Ad) vector encoding green fluorescent protein (GFP). The GFP-positive tumor cells were imaged in vitro and in vivo with a fluorescence stereomicroscope. Using appropriate filters, both GFP fluorescence and adriamycin were simultaneously detected. Nude mice implanted with GFP-positive cells were imaged repeatedly, in a noninvasive manner. RESULTS: SKOV3.ip1 cells infected with Ad-GFP showed high GFP fluorescence, which was eliminated after treatment with adriamycin. Loss of GFP fluorescence was confirmed to be dead cells. For in vivo imaging, intraperitoneal tumors as small as 0.2 mm in diameter were detected externally. Adriamycin uptake was detected in tumors by in vivo imaging, and reduction in tumor size was concurrent with decrease in GFP fluorescence. These findings were confirmed at necropsy. CONCLUSIONS: Fluorescence stereomicroscopy monitored the response of ovarian xenografts to adriamycin therapy. For the first time, GFP and adriamycin were imaged simultaneously.

Detection and measurement of in vitro gene transfer by gamma camera imaging.

The purpose of this work was to develop a high capacity method to image gene transfer to cancer cells growing as monolayers in cell culture plates. A sensitive and high capacity nuclear-imaging method for detection of gene transfer in vitro will allow rapid validation of vectors in different cell lines under various conditions. Human cancer cell lines (A-427 non-small cell lung, SKOV3.ip1 ovarian, MDA-MB-468 breast, and BxPC-3 pancreatic) were infected with a replication-incompetent adenoviral vector encoding the human type 2 somatostatin receptor (Ad-hSSTr2). Expression of the hSSTr2 reporter protein in cells was detected by imaging an internalized 99mTc-labeled, hSSTr2 binding peptide (P2045, Diatide, Inc.). Imaging provided an accurate measure of internally bound 99mTc as evidenced by equivalence of results for imaging region of interest (ROI) analyses and gamma counter measurements. Internally bound 99mTc-P2045 was linearly correlated (R2 = 0.98) with the percentage of hSSTr2-positive cells following gene transfer. Excess P2045 blocked binding and internalization of the 99mTc-P2045, indicating the specificity of the technique. Up to four 96-well plates could be imaged simultaneously, thereby demonstrating the high capacity of the system. This novel in vitro approach provides a new method to test enhanced gene transfer as new vectors are developed.

Simultaneous evaluation of dual gene transfer to adherent cells by gamma-ray imaging.

A gamma camera imaging method was developed to detect dual gene transfer to adherent cells growing as monolayers in cell culture plates. Human cancer cells were infected with replication-incompetent adenoviral vectors encoding the human type 2 somatostatin receptor (Ad-hSSTr2) and/or herpes virus thymidine kinase (Ad-TK). The hSSTr2 and TK reporter proteins were detected by imaging internally bound (99m)Tc-P2045 peptide (Diatide, Inc.) and radioiodinated 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-iodouracil (FIAU), respectively. Following gene transfer, expression of hSSTr2 and TK were accurately imaged in vitro.

Large carotid sheath parathyroid adenoma localized by Tc-99m sestamibi.

The use of Tc-99m sestamibi to localize parathyroid adenomas is well established. Its greatest value is in the detection of adenomas in presurgical candidates to localize one or more adenomas in the parathyroid glands or to identify ectopic parathyroid adenomas. The authors describe a patient who had long-standing hyperparathyroidism with a history of end-stage renal disease, hypertension, and peptic ulcers with gastrointestinal bleeding. The scan showed a large ectopic parathyroid adenoma in the left retrosternocleidomastoid region. At surgery, the adenoma was located between the jugular vein and the carotid artery, within the carotid sheath.

Use of neuroimaging to understand abnormal pain sensitivity in fibromyalgia.

This paper examines the use of neuroimaging to measure change in regional cerebral blood flow (rCBF) produced by pain in patients with fibromyalgia and in healthy individuals. Fibromyalgia patients differ from healthy persons in rCBF distribution in several brain structures involved in pain processing and pain modulation both at rest and during experimental pain induction. These abnormalities may contribute to abnormal pain sensitivity as well as the maladaptive pain behaviors that characterize many patients with fibromyalgia. We anticipate that future neuroimaging studies will enhance our understanding of abnormal pain sensitivity and of pain management interventions aimed at altering central nervous system function in patients with fibromyalgia.

Noninvasive monitoring of gene transfer using a reporter receptor imaged with a high-affinity peptide radiolabeled with 99mTc or 188Re.

UNLABELLED: Gene therapy protocols require better modalities to monitor the location and level of transferred gene expression. One potential in vivo mechanism to assess gene expression would be to image the binding of a radiolabeled peptide to a reporter receptor that is expressed in targeted tissues. This concept was tested in a tumor model using a replication-incompetent adenoviral vector encoding the human type 2 somatostatin receptor (Ad5-CMVhSSTr2). Expression of the hSSTr2 reporter was imaged using a radiolabeled, somatostatin-avid peptide (P829). METHODS: Bilateral subcutaneous A427 tumor xenografts were established on the flanks of athymic nude mice. These human-origin, non-small cell lung tumors are normally negative for hSSTr2 expression. One tumor was injected directly with Ad5-CMVhSSTr2, whereas the second tumor was injected directly with a control Ad5 vector. The mice were injected intravenously 48 h later with P829 peptide that was radiolabeled to high specific activity with 99mTc (half-life, 6 h) or 188Re (half-life, 17 h). Tumors were frozen and evaluated for somatostatin receptor expression using fluorescein-labeled somatostatin. RESULTS: The accumulation of radiolabeled P829 in hSSTr2-expressing tumors was easily visualized by gamma camera imaging 3 h after injection. Imaging region of interest analyses and biodistribution studies confirmed a 5- to 10-fold greater accumulation of both radiolabeled P829 peptides in the Ad5-CMVhSSTr2-injected tumors versus control tumors injected with control Ad5 vectors. Ad5-CMVhSSTr2-injected tumors accumulated 2.5-3.8 percentage injected dose per gram 3 h after injection. Only Ad5-CMVhSSTr2-injected tumors expressed somatostatin receptors, as determined by immunohistochemistry. CONCLUSION: These studies show the feasibility of imaging a 99mTc-labeled peptide's binding to a reporter receptor after in vivo gene transfer to tumor cells. The 188Re-labeled peptide worked equally well for this imaging approach and offers the additional advantage of energetic beta decay with potential therapeutic efficacy. 99mTc and 188Re are generator produced, an advantage for widespread availability and low cost, and both radioisotopes can be imaged with existing, high-resolution modalities. There is great potential for using 99mTc-labeled peptides for imaging gene transfer with the hSSTr2 reporter receptor, especially when the reporter correlates with the expression of therapeutic genes that can be included simultaneously in the gene therapy vector.

A new semiquantitative method for comparing brain tumor uptake of Tc-99m sestamibi and TI-201.

PURPOSE: We describe a new method for measuring brain tumor uptake of TI-201 and Tc-99m sestamibi (MIBI) that permits the semiquantitative comparison of tracer uptake to yield comparable "tumor bulk" ratios. We tested this method in patients treated recently and remotely with chemotherapy to determine if this method could identify differences between these two patient groups. METHODS: Eleven patients with high-grade astrocytoma underwent TI-201 and Tc-99m MIBI SPECT. Each patient received 5 mCi TI-201 intravenously followed by SPECT using a dual-head gamma camera. This was immediately followed by an intravenous injection of 20 mCi Tc-99m MIBI and repeated SPECT. Four patients had recent therapy (from 1 day to 6 weeks before SPECT) and seven had remote treatment (>1 year before SPECT). Regions of interest were outlined in the tumor area using a computer-automated program to include all counts above background activity. Tumor activity counts were obtained from this region of interest. The tumor region of interest was mirrored to the contralateral uninvolved cerebral hemisphere to obtain background control count activity. A hypothetical volume of the number of pixels with background count activity necessary to constitute the tumor count activity (tumor bulk) was calculated using the ratio of total tumor counts (Ct), subtracting background (Cb), and dividing by the average counts per pixel in the control region (Cab). This was multiplied by the number of pixels (P), the pixel volume (Vp), and summed over all sections (i) involved with tumor. This method yields the equation tumor bulk = RESULTS: The mean Tc-99m MIBI to TI-201 tumor bulk ratio was 1.03 (range, 0.81 to 1.12) in four patients who had recently received chemotherapy. The mean Tc-99m MIBI to TI-201 tumor bulk ratio was 1.55 (range, 1.46 to 1.64) in seven patients who had remote therapy. The difference in the Tc-99m MIBI to TI-201 tumor bulk ratio between the two groups was significant (P = 0.0001). Patients who received recent chemotherapy had relatively lower Tc-99m MIBI uptake compared with TI-201. In remotely treated patients, uptake of the Tc-99m MIBI was greater compared with TI-201. CONCLUSION: This method allows semiquantitative comparison of different tracer uptake values independent of tracer dose and reduces the variability in drawing a region of interest when measuring tumor uptake. Among the patients studied, those who had recent chemotherapy showed a low Tc-99m MIBI to TI-201 ratio. This method of measuring "tumor bulk" can provide a useful index of viable tumor size in evaluating early tumor response and during ongoing chemotherapy.

Familial painful restless legs syndrome correlates with pain dependent variation of blood flow to the caudate, thalamus, and anterior cingulate gyrus.

To understand the relationship of caudate, thalamic, and anterior cingulate perfusion to pain states, we investigated familial restless legs syndrome in a father and daughter during the state of pain induced by immobility using semiquantitative regional cerebral blood flow (rCBF) brain single photon emission computed tomography (SPECT). The father underwent 4 brain SPECT scans using the rCBF tracer 99mTc-HMPAO several weeks apart, at different pain levels and after treatment with L-dopa. Caudate, thalamic, and anterior cingulate rCBF indices were measured. The caudate nuclei showed a 13% reduction in rCBF with increasing pain. The thalami and anterior cingulate showed a 7 and 6.6% increase in rCBF, respectively, with increasing pain. Compared to normal controls at rest, there was a decrease in caudate rCBF by 13% and an increase in thalamic rCBF by 3%. Linear regression for the caudate nuclei revealed a significant reduction in rCBF (p < 0.05), as pain increased. The daughter underwent an identical rCBF brain SPECT scan procedure at a high pain level induced by immobilization. Her scan showed a 12% reduction in caudate rCBF and a 1.2% increase in the anterior cingulate rCBF compared to healthy controls. The study supports the association between pain and decreased regional cerebral blood flow to the caudate nucleus as reported in fibromyalgia syndrome. There is increase in anterior cingulate rCBF with increasing pain. Our findings also corroborate that there is increased thalamic rCBF with pain stimulation.

Imaging and tissue biodistribution of 99mTc-labeled adenovirus knob (serotype 5).

Hepatic sequestration of systemically administered adenoviral vectors reduces the number of viral particles available for delivery to other tissues. The biological basis of this phenomenon was investigated using a new in vivo technique which permitted imaging in real time. Recombinant adenovirus serotype 5 knob (Ad5K) was radiolabeled with the gamma-emitter 99mTc (half-life = 6 h). Scatchard analysis of the 99mTc-Ad5K showed specific, high-affinity binding to U293 cells (Kd = 1.4 +/- 0.5 nM), demonstrating that the radiolabeling process had no effect on receptor binding. In vivo dynamic imaging with an Anger gamma camera revealed that the liver binding followed an exponential rise to maximum, with a measured 100% extraction efficiency. Initially, the liver binding capacity was 3.1 +/- 0.4 micrograms Ad5K, equivalent to approximately 17,000 Ad5K molecules per liver cell. Liver binding was blocked by preincubation of Ad5K with neutralizing anti-Ad5K antibody; a 50% reduction in liver uptake was demonstrated by imaging. Unlabeled Ad5K was more effective in blocking liver uptake of 99mTc-Ad5K, whereas irrelevant unlabeled Ad3K had no effect. Imaging data for the liver uptake studies were in agreement with biodistribution determined by removing and measuring tissues. These data demonstrated that in vivo imaging is a sensitive tool for measuring changes to liver tropism. Similar imaging techniques can be applied to adenovirus vectors to measure specific targeting for gene therapy.

Abnormal functional activity of the central nervous system in fibromyalgia syndrome.

The evaluation of pain is one of the major problems facing general practitioners and specialists in medicine. Although the source of pain can be usually be traced to specific abnormalities in a given organ system, some patients present with generalized pain syndromes, such as fibromyalgia, for which no specific source can be found. Some researchers have begun to consider that although there may be a somatic source of such pain at its initiation, over time the pain may be maintained or exacerbated by functional alterations in critical regions of the brain and spinal cord that are involved in pain processing or pain inhibition. This article describes the techniques currently used to measure regional cerebral blood flow (rCBF) in the brain by single photon emission computed tomography (SPECT) imaging, and reviews the SPECT and positron emission tomography literature concerning alterations in functional brain activity associated with pain in healthy individuals and in patients with chronic pain, including those with fibromyalgia. The article concludes by describing the implications of current knowledge about pain and abnormal functional brain activity in the understanding of the pathophysiology of fibromyalgia and in the development of therapeutic strategies to manage patients with this disorder.

Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels.

OBJECTIVE: To determine if regional cerebral blood flow (rCBF) in the left and right hemithalami or the left and right heads of the caudate nucleus is abnormal in women with fibromyalgia (FM). METHODS: Resting-state rCBF in the hemithalami and left and right heads of the caudate nucleus of 10 untreated women with FM and 7 normal control women was measured by single-photon-emission computed tomography. Pain threshold levels at tender and control points also were assessed in both the women with FM and the controls. RESULTS: The rCBF in the left and right hemithalami and the left and right heads of the caudate nucleus was significantly lower in women with FM than in normal controls (P = 0.01, P = 0.003, P = 0.01, and P = 0.02, respectively). Compared with controls, the women with FM also were characterized by significantly lower cortical rCBF (P = 0.001) and lower pain threshold levels at both tender points (P = 0.0001) and control points (P = 0.0001). CONCLUSION: The findings of low rCBF and generalized low pain thresholds support the hypothesis that abnormal pain perception in women with FM may result from a functional abnormality within the central nervous system.

A reference method for correlation of anatomic and functional brain images: validation and clinical application.

We describe a reference device that provides accurate correlation between anatomic and functional brain images. The reference device, which generates fiduciary reference points on sequential scan planes, is positioned adjacent to the canthomeatal line of the subject and held in place by a glasses-like framework anchored to the external auditory meatus. The reference system was tested on 17 subjects undergoing 99mTc hexamethylpropylene amine oxime ([99mTc]HMPAO) brain single-photon emission computed tomography (SPECT) and cranial computed tomography (CT) scans. The centers of the caudate nuclei, thalami, brain stem, and cerebellar vermis were identified independently on CT and SPECT. The average difference +/- 1 SD between structure locations (x, y, and z) on SPECT and CT were calculated as 1.86 +/- 1.5, 2.16 +/- 1.4, and 1.83 +/- 1.9 mm, respectively. The clinical application of the method is showed by coregistration of images from SPECT to MRI. An example of sequential [99mTc]HMPAO brain SPECT scan sections precisely coregistered with MRI scan sections oriented parallel to and sequentially above the canthomeatal line illustrates the correlation between regional cerebral blood flow (rCBF) tracer activity on SPECT and normal anatomic structures. Test-retest activation paradigms in brain SPECT requires precise SPECT-to-SPECT image coregistration to evaluate changes in rCBF during activation. Precisely coregistered rest, 48-hour repeat rest [99mTc]HMPAO SPECT studies are shown to illustrate the normal intrasubject variability of tracer uptake. An example of the usefulness of image coregistration for evaluation of viable residual brain tumor and its application to tumor biopsy is presented. An example of developmental abnormalities identified by [99mTc]HMPAO brain SPECT is illustrated by a case of autistic disorder. An example of image coregistration in stroke and evaluation of cerebrovascular disease with Diamox (Lederle Laboratory Division, Pearl River, NY) cerebrovasculature stress testing is presented. The usefulness in epilepsy using a protocol whereby the tracer is injected during the ictal phase of seizure is presented. We conclude that the reference system provides an accurate, rapid, and noninvasive patient-specific method for correlating brain structure with brain function.

Validation of a reference method for correlation of anatomic and functional brain images.

We describe a reference device that provides accurate correlations between anatomic and functional brain images. The reference device, which generates fiduciary reference points on sequential scan planes, is positioned adjacent to the orbitomeatal line of the subject, and held in place by a framework anchored to the external auditory meatus. The reference system was tested on 17 subjects undergoing Tc-99m-hexamethylpropyleneamine oxime (Tc-99m-HM-PAO) brain single photon emission computed tomography (SPECT) and cranial computed tomography (CT) scans. The centers of the caudate nuclei, thalami, brain stem, and cerebellar vermis were identified independently on CT and SPECT. The average difference +/- 1 sd between structure locations (x, y, and z) on SPECT and CT were calculated as 1.86 +/- 1.5, 2.16 +/- 1.4, and 1.83 +/- 1.9 mm, respectively. The relevance of the method to clinical applications is illustrated by the localization of a recurrent viable glioma and an epileptogenic focus. This reference system provides an accurate, rapid, and noninvasive patient-specific method for the correlation of brain structure with brain function.

Ictal single-photon emission computed tomography demonstrates localized epileptogenesis in cortical dysplasia.

We investigated the use of ictal single-photon emission computed tomography (SPECT) in 2 children with intractable epilepsy. Ictal scalp electroencephalographic studies failed to localize the epileptic focus and interictal data demonstrated widespread lateralized abnormalities. Ictal SPECT studies with technetium 99m-hexamethylpropyleneamineoxime demonstrated focal areas of hyperperfusion in the frontal lobes. Resection of the abnormal areas shown by SPECT was carried out despite evidence of large areas of epileptogenesis demonstrated by scalp and subdural electroencephalographic studies. Pathological material revealed cortical dysplasia. Ictal SPECT provides functional evidence for localized epileptogenesis in focal cortical dysplasia.

Ictal 99mTc HM-PAO brain single-photon emission computed tomography in electroencephalographic nonlocalizable partial seizures.

A 9-year-old child with intractable focal epilepsy was studied for possible surgical treatment. Multiple electroencephalographic studies did not localize the epileptic focus. An ictal single-photon emission computed tomography (SPECT) study with technetium 99m-hexamethylpropyleneamineoxime demonstrated a focal area of hyperperfusion. Through three-dimensional, functional to anatomical image-matching techniques, the focus was overlaid on the magnetic resonance image localizing the cortical convolution responsible for the epileptogenic focus. Subdural electroencephalographic studies performed for seizure localization and functional mapping confirmed this location. This case emphasized the usefulness of ictal SPECT scans in patients with seizures nonlocalizable by electroencephalography being evaluated for epilepsy surgery.

Pre- and post-operative cerebral blood flow changes in subarachnoid haemorrhage.

Assessment of cerebral perfusion on patients with subarachnoid haemorrhage (SAH) in the Neurologic Intensive Care Unit is difficult since nuclear medicine imaging modalities capable of measuring cerebral blood flow (CBF) are not generally available. We performed 101 quantitative (ml 100g-min) bedside CBF measurements on 40 individual patients to correlate SAH grade with CBF and to assess the effect of surgical intervention on CBF. Global CBF (G-CBF) and bihemispheric CBF (B-CBF) asymmetry were correlated with the grade of SAH pre- and post-operatively. Data analysis showed that pre-operative patients with low grade SAH (Hunt and Hess grades 0 to 2) had higher mean G-CBF values [44.2 +/- 71] than those with high grade SAH (Hunt and Hess grades 3 to 4): [mean G-CBF = 34.1 +/- 1.7]. Post-surgery there was a significant improvement in G-CBF; CBF increased [5.3 +/- 1.07] in the group of patients with low grade SAH. Patients with high grade SAH showed no significant improvement in their G-CBF during the first week post-operatively compared to pre-operative values. We conclude that portable units capable of measuring bedside CBF values are useful in monitoring CBF changes in patients with SAH. Patients with low grade SAH have G-CBF within normal limits both pre-operatively and post-operatively, with a statistically significant increase in CBF during two weeks post-operatively. Patients with high grade SAH show no significant increase in CBF one week post-operatively compared to their pre-operative measures.