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.

Estimation of compressed breast thickness during mammography.

To estimate radiation dose during mammography the breast thickness must be known. We present a new method for estimating the thickness of a compressed breast using only the breast image as projected onto a mammogram, calibration data such as the mAs value and image processing techniques. The method proves to be of high accuracy (+/- 0.2 cm for craniocaudal mammograms) and has the advantage over other methods of allowing retrospective estimation of thickness.

Accurate prediction of histologically confirmed Alzheimer's disease and the differential diagnosis of dementia: the use of NINCDS-ADRDA and DSM-III-R criteria, SPECT, X-ray CT, and Apo E4 in medial temporal lobe dementias. Oxford Project to Investigate Memory and Aging.

In a prospective study of more than 200 cases of dementia and 119 controls, annual technetium-99m-hexamethyl-propylene amineoxime (99mTC-HMPAO) single-photon emission computed tomography (SPECT) and annual medial temporal lobe (MTL) oriented X-ray computed tomography (CT) have been used to evaluate the diagnostic potential of functional and structural neuroimaging in the differential diagnosis of dementia. Some subjects have had up to 7 annual evaluations. So far, of 151 who have died, 143 (95%) have come to necropsy. Histology is known for 118, of whom 80 had Alzheimer's disease (AD), 24 had other "non-AD" dementias, and 14 controls with no cognitive deficit in life also had no significant central nervous system pathology. To compare the findings in the dementias with the profile of structural and functional imaging in the cognitively normal elderly, scan data from 105 living, elderly controls without cognitive deficit have also been included in the analysis. All clinical diagnoses were according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; DSM-III-R) criteria, and all histopathological diagnoses according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. Early data from this cohort have suggested that the combination of both MTL atrophy seen on CT with parietotemporal hypoperfusion on SPECT may predict the pathology of AD. The diagnostic sensitivity, specificity, accuracy, and positive and negative predictive values of the NINCDS-ADRDA and DSM-III-R criteria could be assessed in this cohort against the gold standard of histopathology. The diagnostic potential of CT evidence of MTL atrophy alone, SPECT evidence of parietotemporal hypoperfusion alone, and the combination of both of these scan changes in the same individual could then be compared against the diagnostic accuracy of clinical operational criteria in the pathologically confirmed cases. Furthermore, all of these modalities could be compared with the diagnostic accuracy of apolipoprotein E4 (Apo E4) genotyping to predict AD in the histopathologically confirmed cohort. In this population, NINCDS "probable-AD" was 100% specific, 49% sensitive, and 66% accurate; "possible-AD" was only 61% specific, but 93% sensitive and 77% accurate; and the combination of both "probable-AD" and "possible-AD" was 61% specific, 96% sensitive, and 85% accurate. DSM-III-R criteria were 51% sensitive, 97% specific, and 66% accurate. In the same cases and including the 105 living, elderly controls, the diagnostic accuracy of the Oxford Project to Investigate Memory and Aging (OPTIMA) scanning criteria showed CT alone to be 85% sensitive, 78% specific, and 80% accurate; SPECT alone had 89% sensitivity, 80% specificity, and 83% accuracy; and the combination of the two was 80% sensitive, 93% specific, and 88% accurate. The Apo E4 genotype was 74% sensitive but yielded 40% false positives in the histologically confirmed series. The diagnostic accuracy afforded by this method of CT and SPECT used alone is better than that of any established clinical criteria and reveals that the combination of MTL atrophy and parietotemporal hypoperfusion is common in AD, much less common in other dementias, and rare in normal controls. In the NINCDS-ADRDA criteria "possible-AD" cases, the combination of CT and SPECT findings alone were better in all diagnostic indices than the presence of Apo E4 alone in predicting AD. The frequent occurrence of MTL atrophy in AD and also in other "non-AD" dementias later in the course of the disease suggests the concept of medial temporal lobe dementia. This could explain some of the overlap of clinical profiles in the dementias, particularly as the dementia progresses, making clinical differential diagnosis difficult. In this context, the use of SPECT can significantl

Accurate prediction of histologically confirmed Alzheimer's disease and the differential diagnosis of dementia: the use of NINCDS-ADRDA and DSM-III-R criteria, SPECT, X-ray CT, and APO E4 medial temporal lobe dementias. The Oxford Project to Investigate Memory and Aging.

In a prospective study of more than 200 cases of dementia and 119 controls, annual technetium-99m-hexamethyl-propylene amineoxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) and annual medial temporal lobe (MTL) oriented X-ray computed tomography (CT) have been used to evaluate the diagnostic potential of functional and structural neuroimaging in the differential diagnosis of dementia. Some subjects have had up to 7 annual evaluations. So far, of 151 who have died, 143 (95%) have come to necropsy. Histology is known for 118, of whom 80 had Alzheimer's disease (AD), 24 had other "non-AD" dementias, and 14 controls with no cognitive deficit in life also had no significant central nervous system pathology. To compare the findings in the dementias with the profile of structural and functional imaging in the cognitively normal elderly, scan data from 105 living, elderly controls without cognitive deficit have also been included in the analysis. All clinical diagnoses were according to National Institute of Neurological and Communicable Disease and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; DSM-III-R) criteria, and all histopathological diagnoses according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. Early data from this cohort have suggested that the combination of both MTL atrophy seen on CT with parietotemporal hypoperfusion on SPECT may predict the pathology of AD. The diagnostic sensitivity, specificity, accuracy, and positive and negative predictive values of the NINCDS-ADRDA and DSM-III-R criteria could be assessed in this cohort against the gold standard of histopathology. The diagnostic potential of CT evidence of MTL atrophy alone, SPECT evidence of parietotemporal hypoperfusion alone, and the combination of both of these scan changes in the same individual could then be compared against the diagnostic accuracy of clinical operational criteria in the pathologically confirmed cases. Furthermore, all of these modalities could be compared with the diagnostic accuracy of apolipoprotein E4 (Apo E4) genotyping to predict AD in the histopathologically confirmed cohort. In this population, NINCDS "probable-AD" was 100% specific, 49% sensitive, and 66% accurate; "possible-AD" was only 61% specific, but 93% sensitive and 77% accurate; and the combination of both "probable-AD" and "possible-AD" was 61% specific, 96% sensitive, and 85% accurate. DSM-III-R criteria were 51% sensitive, 97% specific, and 66% accurate. In the same cases and including the 105 living, elderly controls, the diagnostic accuracy of the Oxford Project to Investigate Memory and Aging (OPTIMA) scanning criteria showed CT alone to be 85% sensitive, 78% specific, and 80% accurate; SPECT alone had 89% sensitivity, 80% specificity, and 83% accuracy; and the combination of the two was 80% sensitive, 93% specific, and 88% accurate. The Apo E4 genotype was 74% sensitive but yielded 40% false positives in the histologically confirmed series. The diagnostic accuracy afforded by this method of CT and SPECT used alone is better than that of any established clinical criteria and reveals that the combination of MTL atrophy and parietotemporal hypoperfusion is common in AD, much less common in other dementias, and rare in normal controls. In the NINCDS-ADRDA criteria "possible-AD" cases, the combination of CT and SPECT findings alone were better in all diagnostic indices than the presence of Apo E4 alone in predicting AD. The frequent occurrence of MTL atrophy in AD and also in other "non-AD" dementias later in the course of the disease suggests the concept of medial temporal lobe dementia. This could explain some of the overlap of clinical profiles in the dementias, particularly as the dementia progresses, making clinical differential diagnosis difficult. In this context, the use of SPECT can significantly e

Mammographic image analysis.

We describe our recent progress aimed at computer analysis of mammograms. The overall aim is to provide the clinician with reliable quantitative information. We summarise a representation we have developed of the 'interesting' (non-adipose) tissue in a breast, then put the representation to work in three ways: (i) to propose a new quantitative measure to aid in diagnosing masses; (ii) to explore the possibility of reducing by half the radiation dose required for a mammogram; and (iii) recalling some of the results that can be provided by differential compression mammography, in which mammograms are taken at two slightly different compressions.

Kinetics and dosimetry of thallium-201 in human testes.

UNLABELLED: Thallous chloride (201Tl) is a well-known imaging agent. It has been shown to accumulate in the testes. In view of this, the testicular kinetics of 201Tl is investigated in humans and the absorbed dose to the organ calculated. METHODS: Thallous chloride 201Tl was injected intravenously into four patients for myocardial perfusion studies. After clinical evaluation, the testicular uptake and clearance of 201Tl were monitored for about 1 wk using a gamma camera. RESULTS: Testicular uptake of 201Tl was rapid with a mean biological uptake half-time of 0.67 hr and mean biological clearance half-time of 280 hr. The mean maximum testicular uptake of 201Tl was about 0.4% of the injected activity. These data were utilized to calculate the average absorbed dose to the testes. The absorbed dose to the testes was calculated to be 3.5 x 10(-4) Gy/MBq (1.3 rad/mCi) of injected activity. CONCLUSION: When the relative biological effectiveness of the Auger emitter 201Tl is taken into account, the equivalent dose to the testes is 9.5 x 10(-4) Sv/MBq (3.5 rem/mCi).

Computing the scatter component of mammographic images.

The authors build upon a technical report (Tech. Report OUEL 2009/93, Engng. Sci., Oxford Uni., Oxford, UK, 1993) in which they proposed a model of the mammographic imaging process for which scattered radiation is a key degrading factor. Here, the authors propose a way of estimating the scatter component of the signal at any pixel within a mammographic image, and they use this estimate for model-based image enhancement. The first step is to extend the authors' previous model to divide breast tissue into "interesting" (fibrous/glandular/cancerous) tissue and fat. The scatter model is then based on the idea that the amount of scattered radiation reaching a point is related to the energy imparted to the surrounding neighbourhood. This complex relationship is approximated using published empirical data, and it varies with the size of the breast being imaged. The approximation is further complicated by needing to take account of extra-focal radiation and breast edge effects. The approximation takes the form of a weighting mask which is convolved with the total signal (primary and scatter) to give a value which is input to a "scatter function", approximated using three reference cases, and which returns a scatter estimate. Given a scatter estimate, the more important primary component can be calculated and used to create an image recognizable by a radiologist. The images resulting from this process are clearly enhanced, and model verification tests based on an estimate of the thickness of interesting tissue present proved to be very successful. A good scatter model opens the was for further processing to remove the effects of other degrading factors, such as beam hardening.

The indeterminate breast mass: assessment using contrast enhanced magnetic resonance imaging.

Magnetic resonance imaging of the breast was performed on 25 lesions in 24 patients. These lesions were indeterminate on clinical and mammographic examination. The imaging findings were compared with pathological results in all cases. Conventional T1 and T2 spin echo images provided a certain diagnosis in only one case. The pattern of signal enhancement following gadolinium diethylamine triamine pentaacetic acid injection as demonstrated by a T1-weighted gradient recalled echo sequence permitted accurate diagnosis of four recurrent carcinomas and 19 cases of non-malignant disease (17 postoperative scars and two cases of benign breast disease). One false positive diagnosis of cancer was made in a case of fibroadenoma. Dynamic contrast enhanced magnetic resonance imaging may have a role in the assessment of the indeterminate breast mass.

Association of atrophy of the medial temporal lobe with reduced blood flow in the posterior parietotemporal cortex in patients with a clinical and pathological diagnosis of Alzheimer's disease.

A combination of medial temporal lobe atrophy, shown by computed tomography, and reduced blood flow in the parietotemporal cortex, shown by single photon emission tomography, was found in 86% (44/51) of patients with a clinical diagnosis of senile dementia of the Alzheimer type (SDAT). The same combination of changes was found in four out of 10 patients with other clinical types of dementia and in two out of 18 with no evidence of cognitive deficit. Of the 12 patients who died, 10 fulfilled histopathological criteria for Alzheimer's disease, nine of them having a clinical diagnosis of SDAT, and one a clinical diagnosis of multi-infarct dementia. All 10 patients with histopathologically diagnosed Alzheimer's disease had shown a combination of hippocampal atrophy and reduced parietotemporal blood flow in life. In 10 patients (nine with SDAT) out of 12 in whom the hippocampal atrophy was more noticeable on one side of the brain than on the other the parietotemporal perfusion deficit was also asymmetrical, being greater on the side showing more hippocampal atrophy. These results suggest that the combination of atrophy of the hippocampal formation and reduced blood flow in the parietotemporal region is a feature of dementia of the Alzheimer type and that the functional change in the parietotemporal region might be related to the loss of the projection neurons in the parahippocampal gyrus that innervate this region of the neocortex.

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.

Effect of central cholinergic stimulation on regional cerebral blood flow in Alzheimer disease.

Patients with Alzheimer disease (AD) had reduced regional cerebral blood flow (rCBF) in the posterior parietotemporal region compared with controls, as determined with technetium-99m hexamethyl propyleneamine oxime and single photon emission tomography. Central cholinergic stimulation with physostigmine produced a focal increase in rCBF in the posterior parietotemporal region in the patients with AD but not in controls.

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.

Measurement of glomerular filtration rate in homozygous sickle cell disease: a comparison of 51Cr-EDTA clearance, creatinine clearance, serum creatinine and beta 2 microglobulin.

Glomerular filtration rates (GFR) were measured with 51Cr-EDTA in 38 patients (aged 40-75 years) with homozygous sickle cell disease and compared with serum beta 2 microglobulin concentrations in 38 patients and with creatinine clearance in 21 patients. GFR estimated with 51Cr-EDTA was closely correlated with single serum creatinine measurements and the inverse of serum beta 2 microglobulin. Creatinine clearance was also found to be correlated, but values were, on average, 32% below those obtained by the 51Cr-EDTA method, and this difference was significant. It is concluded that measurements of beta 2 microglobulin, single serum creatinine, and creatinine clearance are valuable indicators of GFR in homozygous sickle cell disease. Measurement of beta 2 microglobulin was a useful and reliable method of estimating GFR from single plasma measurements and is therefore a useful means of screening the population.

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.