Clinical characteristics and brain PET findings in 3 cases of dissociative amnesia: disproportionate retrograde deficit and posterior middle temporal gyrus hypometabolism.

BACKGROUND: Precipitated by psychological stress, dissociative amnesia occurs in the absence of identifiable brain damage. Its clinical characteristics and functional neural basis are still a matter of controversy. METHODS: In the present paper, we report 3 cases of retrograde autobiographical amnesia, characterized by an acute onset concomitant with emotional/neurological precipitants. We present 2 cases of dissociative amnesia with fugue (cases 1 and 2), and one case of focal dissociative amnesia after a minor head trauma (case 3). The individual case histories and neuropsychological characteristics are reported, as well as the whole-brain voxel-based 18FDG-PET metabolic findings obtained at group-level in comparison to 15 healthy subjects. RESULTS: All patients suffered from autobiographical memory loss, in the absence of structural lesion. They had no significant impairment of anterograde memory or of executive function. Impairment of autobiographical memory was complete for two of the three patients, with loss of personal identity (cases 1 and 2). A clinical recovery was found for the two patients in whom follow-up was available (cases 2 and 3). Voxel-based group analysis highlighted a metabolic impairment of the right posterior middle temporal gyrus. 18FDG-PET was repeated in case 3, and showed a complete functional brain recovery. CONCLUSION: The situation of dissociative amnesia with disproportionate retrograde amnesia is clinically heterogeneous between individuals. Our findings may suggest that impairment of high-level integration of visual and/or emotional information processing involving dysfunction of the right posterior middle temporal gyrus could reduce triggering of multi-modal visual memory traces, thus impeding reactivation of aversive memories.

Unilateral surgery for primary hyperparathyroidism on the basis of technetium Tc 99m sestamibi and iodine 123 subtraction scanning.

HYPOTHESIS: Parathyroid scanning, based on simultaneous recording of technetium Tc 99m sestamibi and iodine 123 images, is able to identify patients with multiple parathyroid gland disease and is a safe imaging technique for unilateral parathyroid surgery. DESIGN: Scintigraphic criteria of eligibility for unilateral surgery were prospectively tested against findings of conventional bilateral surgery. SETTING: Patients referred to an endocrine surgeon in a university hospital. PATIENTS: Seventy consecutive patients with primary hyperparathyroidism had dual-isotope scanning before conventional surgery. Forty-one patients had scan findings compatible with unilateral surgery, with a single focus of high intensity seen on the anterior and lateral views. The remaining 29 patients had 1 or more criteria of ineligibility: (1) scan findings pointing to multiple gland disease, (2) no well-identified focus, (3) contralateral thyroid nodule requiring surgical management, or (4) family history of hyperparathyroidism or multiple endocrine disease. MAIN OUTCOME MEASURES: Number of enlarged parathyroid glands at surgical inspection and calcemia follow-up. RESULTS: None of the 41 patients, with a single well-defined focus on the scan image, showed evidence of multiple parathyroid involvement. Each parathyroid adenoma was resected from the precise site predicted by the subtraction scan. Nine patients (13%) had surgical findings of multiple parathyroid gland disease. All 9 were ineligible based on preoperative image findings. CONCLUSIONS: Unilateral surgery can be safely offered to 60% of patients with primary hyperparathyroidism, on the basis of simultaneous (99m)Tc-sestamibi and (123)I scanning. This may reduce the length of the operation, anesthesia requirements, and hospital stay, and the risks of hypoparathyroidism and injury to the recurrent laryngeal nerve.

[Surveillance after treatment of differentiated thyroid cancers]. / Surveillance après traitement des cancers thyroïdiens différenciés.

UNLABELLED: The prognosis of differentiated thyroid carcinoma mainly depends on the quality of the initial treatment and on early detection and management of any recurrences. STUDY AIM: The aim of this retrospective study was to assess the modalities and duration of surveillance in these patients according to an original classification based on the initial extent of the tumour. PATIENTS AND METHOD: The modalities of detection of local recurrences and metastases and the date of the latest recurrences were assessed in a series of 509 patients with a mean follow-up of 8.2 years (range: 1 to 25 years). Most patients were treated by total thyroidectomy, followed by a therapeutic dose of radioactive iodine. The other patients with a small localized carcinoma underwent partial thyroidectomy without radioactive iodine. Patients were divided into four groups on the 7th postoperative month after follow-up scintigraphy and thyroglobulin assay: group I: microcancers (n = 117), group II: cancer without lymph node involvement or metastasis and normal thyroglobulin divided into IIA, age < 45 years (n = 100) and IIB, age > 45 (n = 94), group III: cancer with lymph node involvement and normal thyroglobulin (n = 102), group IV: high-risk cancers with metastases or regional extension other than lymph node extension or thyroglobulin > 3 micrograms/L (n = 96). RESULTS: Cancer-dependent actuarial survival rates for groups I, IIA, IIB, III, IV were 100%, 100%, 96%, 100%, and 73% at 10 years and 100%, 100%, 92%, 100%, and 86% at 15 years, respectively. Local or metastatic recurrences were sometimes detected by a single follow-up examination, while the other examinations were negative: cervical palpation, thyroglobulin assay, iodine scintigraphy, chest X-rays. The latest recurrences were observed at 12 years in groups I and IIA and at 16 years in groups IIB, III, and IV with normal thyroglobulin. CONCLUSION: This study confirms the importance of weaning thyroglobulin assays and scintigraphy which must be repeated every 5 years. Cervical palpation, thyroglobulin assay without weaning, chest X-rays may also detect recurrences. Duration of follow-up must be adapted to the initial extension and subsequent course: 15 years in groups I and IIA, 20 years in groups IIB, III, and IV with normal thyroglobulin, for at least 10 years after each recurrence, and life-long in the case of progression and thyroglobulin > 3 micrograms/L. Patients must be informed about the duration of follow-up at the 7th month when the definitive classification can be established and continuity of this follow-up must be documented in a special register.

Preoperative imaging of parathyroid glands with technetium-99m-labelled sestamibi and iodine-123 subtraction scanning in secondary hyperparathyroidism.

BACKGROUND: Parathyroidectomy is unsuccessful in 10-30% of uraemic patients operated on for secondary hyperparathyroidism. We investigated the usefulness of preoperative radionuclide imaging, with simultaneous recording of the distribution images of iodine-123 and technetium-99m-labelled sestamibi. METHODS: 11 patients with secondary hyperparathyroidism underwent prospective imaging and parathyroidectomy. Plasma concentrations of intact parathyroid hormone (PTH) were measured in all patients before and 6 months after subtotal parathyroidectomy. FINDINGS: Preoperative scanning showed 42 hot-spots suggesting enlarged parathyroid glands. 45 glands were discovered at surgery, and the parathyroidectomy was deemed successful in ten patients. Among the latter, one patient had a supernumerary parathyroid gland detected by scanning and resected from the left thymus. Another patient showed ectopic uptake corresponding to a large parathyroid gland in the upper mediastinum, and another had a parathyroid gland well above the thyroid. No false-positive scan findings were documented. In the patient for whom parathyroidectomy failed, preoperative scanning suggested five enlarged parathyroid glands, though the surgeon found only four glands, in their normal positions. Hyperparathyroidism persisted (intact PTH 527 ng/L, 6 months after surgery). A second scan confirmed the preoperative scan, showing a fifth parathyroid gland in the middle of the right thyroid lobe. INTERPRETATION: Simultaneous recording of 99mTc-sestamibi and 123I improved the imaging of parathyroid glands in secondary hyperparathyroidism. The technique can identify ectopic and supernumerary parathyroid glands.

Quantitation in planar renal scintigraphy: which mu value should be used?

The attenuation coefficient value mu used by different authors for quantitation in planar renal scintigraphy varies greatly, from the theoretical value of 0.153 cm-1 (appropriate for scatter-free data) down to 0.099 cm-1 (empirical value assumed to compensate for both scatter and attenuation). For a 6-cm-deep kidney, such variations introduce up to 30% differences in absolute measurement of kidney activity. Using technetium-99m phantom studies, we determined the mu values that would yield accurate kidney activity quantitation for different energy windows corresponding to different amounts of scatter, and when using different image analysis approaches similar to those used in renal quantitation. With the 20% energy window, it was found that the mu value was strongly dependent on the size of the region of interest (ROI) and on whether background subtraction was performed: the mu value thus varied from 0.119 cm-1 (loose ROI, no background subtraction) to 0.150 cm-1 (kidney ROI and background subtraction). When using data from an energy window that could be considered scatter-free, the mu value became almost independent of the image analysis scheme. It is concluded that: (1) when performing background subtraction, which implicitly reduces the effect of scatter, the mu value to be used for accurate quantitation is close to the theoretical mu value; (2) if the acquired data were initially corrected for scatter, the appropriate mu value would then be the theoretical mu value, whatever the image analysis scheme.

Parathyroid imaging using simultaneous double-window recording of technetium-99m-sestamibi and iodine-123.

UNLABELLED: Technetium-99m-sestamibi represents an important advance in the scintigraphic location of parathyroid neoplasms. However, the optimal procedure for 99mTc-sestamibi parathyroid scanning has not been defined. The first objective of this work was to optimize the technical aspects of subtraction scanning, using simultaneous double-window recording of 99mTc-sestamibi and 1231 instead of successive image recording. The second objective was to compare two protocols for detecting abnormal parathyroid glands: subtraction scanning and single-tracer double-phase scanning. METHODS: Thirty patients referred for first surgery of primary hyperparathyroidism had both subtraction scanning and double-phase scanning in the same imaging session. Images of 99mTc-sestamibi and 123I were recorded simultaneously in nonoverlapping windows and then subtracted. For double-phase scanning, images of 99mTc-sestamibi, acquired 15 min and 120 min after tracer injection, were visually compared. Surgery disclosed a solitary adenoma in 27 patients, bilateral adenomata in 2 patients and 3 hyperplastic glands in the last patient. No patient had persistent hypercalcemia. RESULTS: Preoperative 99mTc-sestamibi/123I subtraction scanning located 25 of 27 solitary adenomas, the bilateral adenomata and 3 of 3 hyperplastic glands. The overall sensitivity for enlarged parathyroids was 94%, and the false-positive image rate was 3%. The 99mTc-sestamibi single-tracer technique located 22 of 27 solitary adenomas, the bilateral adenomata and 1 of 3 hyperplastic glands. Overall sensitivity was 79% and the false-positive image rate was 10%. The gamma camera imaging time was 30 min for the subtraction technique and 50 min for the single-tracer double-phase study. An ectopic adenoma in the sheath of the right carotid artery was detected by both techniques. CONCLUSION: These results, together with other data in the literature, indicate that 99mTc-sestamibi/123I subtraction imaging is accurate in locating enlarged parathyroids. Classical difficulties of this technique (motion artifacts and prolonged immobilization) were avoided by using simultaneous recording of the two isotopes. In this series subtraction imaging was more rapid and more sensitive (p < 0.04) than the single-tracer technique.

Secondary hyperparathyroidism: detection with I-123-Tc-99m-Sestamibi subtraction scintigraphy versus US.

PURPOSE: To compare iodine-123-technetium-99m-sestamibi subtraction scintigraphy with ultrasonography (US) for detection of parathyroid abnormalities in uremic patients with secondary hyperparathyroidism. MATERIALS AND METHODS: Fourteen adult uremic patients with severe secondary hyperparathyroidism underwent subtraction scintigraphy before total or subtotal parathyroidectomy. Subtraction scintigrams were acquired with a double-energy-window technique. US was performed with high-frequency transducers and standard methods. RESULTS: 1-123-Tc-99m-sestamibi subtraction scintigraphy correctly demonstrated 41 of 50 surgically confirmed enlarged parathyroids; US demonstrated 27. Sensitivity for detection of hyperplastic glands was 82% for scintigraphy and 54% for US. Scintigrams were correct in seven patients, and US scans were correct in five. Scintigraphy demonstrated all four enlarged parathyroids in six of 12 patients who were to undergo first surgery, whereas US demonstrated all four enlarged glands in three of the 12 patients. Gland weight was correlated with likelihood of detection with either method. Glands undetected at scintigraphy were significantly (P < .01) smaller (mean weight, 257 mg) than those undetected at US (mean weight, 467 mg). CONCLUSION: I-123-Tc-99m-sestamibi subtraction scintigraphy is efficient for detection of enlarged parathyroid glands in uremic patients with secondary hyperparathyroidism and is more sensitive than US.

Primary hyperparathyroidism: higher success rate of first surgery after preoperative Tc-99m sestamibi-I-123 subtraction scanning.

PURPOSE: To evaluate the usefulness and cost-effectiveness of routine preoperative technetium-99m sestamibi-iodine-123 subtraction scanning in patients with parathyroid gland disease. MATERIALS AND METHODS: Tc-99m sestamibi-I-123 subtraction scanning was performed in 65 patients with primary hyperparathyroidism who were referred for evaluation before first surgery. RESULTS: Focal tracer uptake was detected in the mediastinum in two patients who then underwent primary sternotomy; a parathyroid adenoma, anterior to the ascending aorta, was resected in each case. In a third patient, imaging showed tracer uptake above the thyroid gland; this patient underwent resection of an undescended parathyroid adenoma located in the sheath of the right carotid artery. Initial surgery was curative in all patients. Preoperative subtraction scans depicted 56 of 59 (95%) solitary adenomas. Four patients had hyperplasia; two had double adenoma. Imaging findings indicated multiple parathyroid involvement in five of these patients and facilitated location of 12 of 15 (80%) enlarged glands. Four adenomas and two hyperplastic glands that weighed less than 100 mg were detected. The positive predictive value for any suspected location was 96%. Average surgery time was reduced from 120 to 90 minutes. CONCLUSION: Preoperative subtraction scanning is useful in planning parathyroid surgery and appears to be cost-effective.

[Recent progress in radionuclide imaging of parathyroid glands]. / Récents progrès en imagerie scintigraphique des parathyroïdes.

Scintigraphic imaging of parathyroid glands has been the subject of new developments. Efficiency of the technique has been improved by the use of a new agent Tc-99m sestamibi (MIBI). A meta-analysis study of the literature confirmed the superiority of this agent toward the conventional Tc/T1201. Various protocols have been proposed for parathyroid imaging with MIBI they are described with a comparison of their advantages and drawbacks. The superiority of a two isotopes protocol using Tc-99m sestamibi with Iodine 123 and a subtraction processing seems proven. Moreover, this latter protocol allows the use of lateral views resulting in a higher accuracy. The visualization of hyperplasic glands is also improved by this technique. Comparison of ultrasonography versus Tc-99m sestamibi scintigraphy is discussed in the light of recent published materials. The scintigraphy appears more sensitive than ultrasonography and specially in the detection of mediastinal ectopic glands. Finally the exact role of radionuclid imaging of the parathyroids in the management of primary hyperparathyroidism is described.

Cardiac axis change between prone and supine positioning may contribute to differences in 99Tc(m)-MIBI myocardial SPET imaging.

The aims of this study were to assess the effect of prone and supine positioning on 99Tc(m)-MIBI myocardial SPET images and the contribution of cardiac axis change. We compared 227 tomograms of patients imaged in the prone position with 227 tomograms of the same patients imaged in the supine position. For each tomographic session, the axis angle of the heart was recorded using an in-house program. The results showed a significant change in the cardiac axis angle of 9 degrees in the transaxial plane (P < 0.001). This change in the cardiac axis correlated with differences in cardiac wall activity (wall activity when the patient was imaged in the prone position minus wall activity when the patient was imaged in the supine position). Our results suggest that factors other than diaphragmatic movement and attenuation could account for the differences in wall activity observed when patients are imaged prone versus supine. Differences in the intensity of photon attenuation in the heart itself, depending on the cardiac axis, could be a contributing factor. Quantitation of the variation in wall activity leads us to suggest that 99Tc(m)-MIBI SPET should be performed in the prone position to allow better visualization of the inferior and the septal walls. The anterior and lateral walls are better studied in the supine position. Images acquired in both the prone and supine positions would allow the best assessment of all walls.

Subcellular distribution of a new fluorinated, biocompatible, non-ionic telomeric carrier: a study in cultured B16 melanoma and rat skin fibroblasts.

Tris-hydroxymethyl-amino-methane telomers bearing a fluorinated end have recently been proposed as potential drug carriers. Using ion microscopy, we have investigated the cell uptake and subcellular distribution of a perfluorinated telomere, called F-TAC, in two cell lines, malignant murine B16 melanoma and normal rat skin fibroblasts. Single layer cell cultures on gold plates were incubated with F-TAC at different concentrations. Ion microscopy using mass spectrometry enabled the detection of Fluorine 19 atoms entering into F-TAC constitution. This microanalytical study showed an elective cytoplasmic localization of the molecule, wherein the distribution is relatively homogeneous. Within same culture and incubation conditions, intercellular variations in F-TAC content were very low. In the malignant line, the intracellular concentration remains practically identical when increasing F-TAC concentration in the culture medium above 0.2 mg/ml, indicating that the uptake phenomenon is saturable. In conclusion, the F-TAC telomer easily crosses the plasma membrane, however, it has difficulties in crossing the nuclear membrane. It is likely that intracellular penetration is essentially due to rapid endocytosis of the telomer.

Practical aspects of electron energy loss spectroscopy (EELS) in biology.

New commercially available electron microscopes accessories permit an easy Electron Energy Loss Spectroscopy (EELS) analysis with good sensitivity and accuracy. But EELS still remains a complex method whose potentiality is seldomly completely exploited. Beside nanoanalysis, several possibilities of producing new images are described. The scattering power image for beam-sensitive specimens, the separation of elastic and inelastic components and the mean free path ratio are among these possibilities. Mass thickness measurement for example can benefit a lot from these techniques. In the nanoanalysis field, a particular emphasis is given to the spectrum-image acquisition method. This method is very convenient to obtain chemical maps of different elements from the same area of the specimen. The background effects and the errors in its estimation are often underevaluated. This can provoke spurious effects in chemical maps. The spectrum-image offers several ways to avoid this inconveniency.

Factor analysis in successive hepatobiliary imaging of native and transplant livers.

UNLABELLED: A young male suffering from fulminant hepatic failure of unknown origin had an auxiliary partial orthotopic liver transplantation performed. The aim of the present study was to test the performance of factor analysis of medical image sequences (FAMIS) in the post-transplantation monitoring of the graft and native liver functions. METHODS: Four successive hepatobiliary studies within 63 days following transplantation using 99mTc-mebrofenin were performed (on days 13,20,34,63). The 60 one-minute dynamic series were subjected to two successive FAMIS procedures. RESULTS: For all studies, except the first, FAMIS was able to extract three factor couples (factor images and factors or curves) those of the native liver, the graft liver and the biliary region. The factors time evolution in uptake and excretion components showed the correlations between clinical status and scintigraphic results and helped interpretation of biochemical tests. CONCLUSION: The possible utility of systematic liver transplant monitoring by radionuclide hepatobiliary imaging in identification of complications requiring medical or surgical intervention in graft livers was demonstrated. Furthermore, our study showed the functional recovery potential of the native liver in patients suffering from fulminant hepatitis.

New STEM multisignal imaging modes, made accessible through the evaluation of detection efficiencies.

With its specific design for recording simultaneous signals, the scanning transmission electron microscope (STEM) offers unique imaging capabilities. In order to use them fruitfully, we have implemented, on a VG STEM equipped with a magnetic spectrometer, home-made detectors for recording multisignal images. This paper first describes a method developed for the quantitative evaluation of detection efficiency of all data-acquisition channels involved in these multisignal images. At this stage, new imaging modes become accessible, which can be classified following their specificity and sensitivity; scattering power image, elastic and inelastic images mean free path ratio images. Original applications encountered in the biological as well as in the materials science fields illustrate the possibilities of these various approaches, which can be of great interest in quantitative microscopy, analytical imaging or low-dose observation.

Electron energy loss spectroscopy and biology.

Although most of the recent work concerning EELS in electron microscopy is related to instrumental developments, there are a number of papers relating to biological applications. The aim of this paper is to attempt to present in a pedagogical manner the subject of EELS and biology. The biologist will be taught about EELS and the physicist about the possible biological applications of this technique. The paper thus consists of: a presentation of a minimum background on EELS required for biologists to realize what its potential is; a description of why EELS is a useful tool in biology; a description of which kind of biological problems may be resolved through EELS; finally a survey relating to the problems encountered in applying EELS to biology, i.e., specimen preparation, beam damage and artefacts.

How to obtain a thickness-independent image in a STEM.

"Z" contrast is independent of thickness only for extremely thin specimens (3 nm of carbon). Following Egerton [Ultramicroscopy 10 (1983) 293], we propose a new method of imaging which is really independent of thickness and which provides absolute values. It consists of a mixing of the unscattered, the annular darkfield and the inelastic signal. Two-dimensional histograms are used to determine the relative efficiency factors of the different images. Thus, in addition to the obtaining of lambda i/lambda e images, the method allows the calculations of the ratios of the detection factors, of the primary beam intensity image and the production of image free of beam fluctuations. An example of such a treatment is given for a biological specimen with knife-marks.

Unconventional modes for STEM imaging of biological structures.

In this paper recent developments are discussed in instrumentation and methodology associated with scanning transmission electron microscopes (STEM), which are of great potential interest for solving structural and chemical problems in biological specimens. After describing the main features of the instrument, an attempt is made to define which type of signal acquisition and processing is best suited to obtain a given type of information. Starting with a definition of cross sections of interest, a discussion follows of methods using angular selection, energy selection of the transmitted beam, and several ways of signal mixing. More specific attention is devoted to two main modes of processing signals: ratio contrast, which emphasizes slight changes in scattering factors, rather independent of thickness variations; and elemental mapping, which provides semi-quantitative information on the distribution of low Z elements of great significance in biological specimens. Data relevant to typical biological objects are presented and discussed; they allow for the definition of the capabilities and limitations of these methods. These unconventional imaging modes define a new attitude for improving the efficiency of this modern generation of electron microscopes.

Electron energy loss chemical mapping of low Z elements in biological sections.

A STEM VG HB 501 equipped with a Gatan spectrometer has been interfaced to a PDP 11-34 computer. Digital energy filtered images have been recorded with several energy windows on both sides of a characteristic level, so that the exact background can be stripped under the core loss signal for each pixel. Results concern the distribution of nitrogen (K-edge at 402 eV), oxygen (K-edge at 532 eV) and iron (L23 edge at 705 eV) in embedded sections of bone marrow. The present performances of the system allow the detection of composition variations of 1 to 2% for these elements, with a lateral accuracy of the order of 5 nm in a section of 50 nm thickness. Individual ferritin molecules distributed within the section are clearly imaged and analyzed with the characteristic iron edge.