Cerebral perfusion SPET correlated with Braak pathological stage in Alzheimer's disease.

Reductions in regional cerebral perfusion, particularly in the posterior temporo-parietal lobes, are well recognized in Alzheimer's disease. We set out to correlate perfusion changes, using (99m)Tc-HMPAO single photon emission tomography (SPET), with the pathological stage of Alzheimer's disease. The 'Braak stage' of the distribution of neurofibrillary pathology in post-mortem brains was used to classify SPET scans taken in life from a mixed (dementia and control) elderly population into the entorhinal stage (n = 23 subjects), limbic stage (n = 30 subjects) and neocortical stage (n = 36 subjects) Alzheimer's disease pathology. The SPET scans were then registered to a common, standard Talaraich space, and single template scans produced for each pathological stage. Comparison of these templates revealed an evolution in the pattern of reduction in regional perfusion. Additional comparisons were performed using earlier SPET scans obtained 5 years before death. For comparisons between templates, a threshold of 10% perfusion change was chosen so as to be clinically relevant as well as statistically significant. Reduced perfusion appears between the entorhinal and limbic stages in the anterior medial temporal lobe, subcallosal area, posterior cingulate cortex, precuneus and possibly the supero-anterior aspects of the cerebellar hemispheres. Large posterior temporo-parietal perfusion defects then appear between the limbic and neocortical stages, before finally large frontal lobe perfusion defects. The time course of these perfusion defects appears relatively long, suggesting that perfusion changes may have scope to be a diagnostic aid in staging Alzheimer's disease in life. The reduction in anterior medial temporal lobe perfusion may have future relevance on modern high resolution SPET and PET systems and also perfusion-type MRI sequences.

Ocular surface residence times of artificial tear solutions.

Solutions of hydroxypropylmethylcellulose (HPMC) and polyvinyl alcohol (PVA) are widely used as artificial tears. However, their usefulness is limited by the short duration of their effect. Dilute sodium hyaluronate (SH) solutions exhibit non-Newtonian rheology with high viscosities at low shear rates, which would be expected to enhance their ocular surface residence time. Using quantitative gamma scintigraphy, estimates of the ocular surface residence times of 0.3% HPMC, 1.4% PVA, and 0.2% SH were made in six patients with keratoconjunctivitis sicca. The sodium hyaluronate solution had a mean half-life on the ocular surface of 321 s, significantly longer than hydroxypropylmethylcellulose (44 s; p = 0.012) and polyvinyl alcohol (39 s; p = 0.013).

Pentavalent Tc-99m DMSA scintigraphy. Prospective evaluation of its role in the management of patients with medullary carcinoma of the thyroid.

Ten patients with suspected primary, recurrent or metastatic medullary carcinoma of the thyroid (MCT) were studied prospectively with Tc-99m(V) DMSA. Of these, two patients had primary disease, seven patients were asymptomatic but had persistent and serial elevations in serum calcitonin following previous thyroid resections for MCT, and one asymptomatic patient with normal serum calcitonin was studied because of suspected hilar nodes metastases. The serial calcitonin peak in the patients was 0.04-43ng/ml (normal less than 0.08ng/ml). Scintigraphy was considered positive in seven of the asymptomatic patients and equivocal in one. The two patients with primary disease had increased uptake before but not after thyroidectomy. Primary disease, localized recurrence and distant metastases in soft tissue (nine patients) and bone (one patient) were detected in these patients, and this resulted in early surgical resection (five patients) and radiotherapy (one patient). We conclude that Tc-99m(V) DMSA is a useful imaging agent in the evaluation of asymptomatic MCT patients with hypercalcitonemia.

Preclinical detection of metastatic melanoma.

We present a patient with melanoma in whom the performance of combined immunoscintigraphy and immunolymphoscintigraphy indicated the presence of metastatic disease 16 months before clinical manifestation. This approach may be useful in the early detection of metastatic disease and the patient presented is a lesson that cutaneous foci of uptake should not be dismissed as false-positive in the absence of clinical correlation.

Immunoscintigraphy of endometriosis.

Twenty-eight women with suspected endometriosis or infertility, or both, received radiolabelled monoclonal antibody OC-125 F(ab')2 fragments before surgery in a study to determine whether foci of pelvic endometriosis could be displayed with immunoscintigraphy. Immunoscintigraphy was positive in 22 women (16 with endometriosis, two with pelvic adhesions, one with pelvic inflammatory disease and one with normal pelvic findings) and negative in five women (two with endometriosis and three with normal pelvic findings). One woman developed a hypersensitivity reaction and, therefore, did not receive the radiolabelled fragments. The method had 89% sensitivity and 33% specificity for the diagnosis of endometriosis; it had 91% sensitivity and 60% specificity for the diagnosis of benign pelvic disease.

Radioimmunodetection of human melanoma.

Radioimmunodetection has been shown to be an invaluable method in the diagnosis of primary and metastatic malignant disease. Fourteen patients, consisting of four men and 10 women with clinical suspicion of metastatic malignant melanoma or ocular melanoma were prospectively evaluated with the technique. Ten (71%) had positive and four (29%) had negative scintigrams. There was one false-positive scintigram. The overall sensitivity and specificity were 100% and 80%, respectively. SPET was necessary for the radioimmunodetection of patients with ocular melanoma. Combined immunoscintigraphy and immunolymphoscintigraphy enhanced the diagnosis of small, cutaneous melanoma and metastatic lymph node disease.

Precorneal residence times of sodium hyaluronate solutions studied by quantitative gamma scintigraphy.

Sodium hyaluronate solutions have been advocated in the management of a variety of dry-eye states. By virtue of their non-Newtonian rheological properties, formulations exhibiting high zero-shear viscosities may be used as an artificial tear with the expectation of prolonged precorneal residence times and improved tolerance. Quantitative gamma scintigraphy was used to evaluate the residence times of 0.2% and 0.3% sodium hyaluronate solutions and a polymer-free solution of buffered saline in 12 patients with keratoconjunctivitis sicca and a group of six normal volunteers. Using several indices of residence time, mean values for the sodium hyaluronate solutions were significantly longer than those for buffered saline. Parallel changes in tear film thickness were also demonstrated using a technique based on laser interferometry.

Medullary carcinoma of the thyroid: management of persistent hypercalcitonaemia utilizing [99mTc] (v) dimercaptosuccinic acid scintigraphy.

Whole body scintigraphy with [99mTc] (v)dimercaptosuccinic acid (pentavalent DMSA) was performed in seven patients with histologically confirmed medullary carcinoma of the thyroid (MCT). Six of these patients had undergone previous thyroid resections for MCT and, although asymptomatic at the time of pentavalent DMSA scintigraphy, had persistent and serial elevations in their plasma calcitonin levels. One additional patient was scanned before and after total thyroidectomy for MCT. The pentavalent DMSA scintigram demonstrated either local neck recurrence (three patients) or distant metastases (two patients) in five of the six asymptomatic patients. In one asymptomatic patient only equivocal neck uptake was demonstrated. Since he had only minimal calcitonin elevations, repeat neck exploration was not performed. The one patient studied before thyroid resection for MCT demonstrated neck uptake before, but not after, total thyroidectomy. The results of the scintigrams had significant impact on patient care and resulted in neck re-exploration (three patients), neck biopsy (one patient), and lumbar spine biopsy and subsequent radiotherapy (one patient). These data demonstrate pentavalent DMSA to be a sensitive localizing agent in the evaluation of asymptomatic MCT patients with hypercalcitonaemia. Accurate targeting of treatment may be shown in due course to have a beneficial impact on survival.

Immunoscintigraphy of ovarian endometriosis. A preliminary study.

CA-125 is a membrane antigen detected in the serum of some women with gynaecological disease including endometriosis. We attempted to use a radioiodinated anti-CA-125 monoclonal antibody, OC-125, to image ovarian endometriosis using immunoscintigraphy. Two women with significant endometriosis and normal serum CA-125 levels had positive immunoscintigraphy. In one woman, all areas of endometriosis were imaged; in the other, endometriosis in one affected ovary was seen, but uptake in the other ovary was less than the extent of the disease.

Failure of cerebral autoregulation as a cause of brain dysfunction in the elderly.

Cerebral blood flow in relation to change in arterial pressure was measured in 11 elderly patients with postural hypotension. Seven patients with symptoms showed bilateral or unilateral failure of cerebral autoregulation, while the four asymptomatic patients did not. Variations in cerebral autoregulation would explain why some elderly people with minor falls of systemic arterial pressure develop clinical signs of cerebral ischaemia whereas others with greater falls in blood pressure remain asymptomatic. Elderly patients with impaired autoregulation may be at risk of brain damage from minor falls in blood pressure.