MRI dynamic color mapping: a new quantitative technique for imaging soft tissue motion in the orbit.

PURPOSE: To investigate both feasibility and clinical potential of magnetic resonance imaging-dynamic color mapping (MRI-DCM) in measuring the motion of soft tissues in the orbit and in the diagnosis of orbital disorders by detecting changes in motion. METHODS: Sequences of MRI scans were acquired (acquisition time, 5 seconds) in a shoot-stop manner, while the patient fixated at a sequence of 13 gaze positions (8 degrees intervals). Motion was quantified off-line (in millimeters per degree of gaze change) using an optical flow algorithm. The motion was displayed in a color-coded image in which color saturation of a pixel shows the displacement and the hue the displacement's orientation. Six healthy volunteers and four patients (two with an orbital mass and two with acrylic ball implant after enucleation) were studied. RESULTS: The technique was found to be clinically feasible. For a gaze change of 1 degrees, orbital tissues moved between 0.0 and 0.25 mm/deg, depending on the type of tissue and location in the orbit. In the patients with an orbital mass, motion of the mass was similar to that of the medial rectus muscle, suggesting disease of muscular origin. In the enucleated orbits, soft tissue motion was decreased. One eye showed attachment of the optic nerve to the implant, which could be verified by biopsy. CONCLUSIONS: MRI-DCM allows noninvasive and quantitative measurement of soft tissue motion and the changes in motion due to pathologic conditions. In cases in which the diagnosis of a tumor in the apex is in doubt, it may reduce the need for biopsy. In contrast to static computed tomographic (CT) scans and MRIs, it can differentiate between juxtaposition and continuity and may be a new and promising tool in the differential diagnosis of intraorbital lesions.

Vascularization of head and neck paragangliomas: comparison of three MR angiographic techniques with digital subtraction angiography.

BACKGROUND AND PURPOSE: MR angiography of the head and neck region has been studied widely, but few studies have been performed concerning the efficacy of MR angiography for the identification of the specific vascular supply of the highly vascular head and neck paragangliomas. In this study, we compared three MR angiography techniques with respect to visualization of branch arteries in the neck and identification of tumor feeders in patients with paragangliomas. METHODS: Fourteen patients with 29 paragangliomas were examined at 1.5 T using 3D phase-contrast (PC), 2D time-of-flight (2D TOF), and multi-slab 3D TOF MR angiography. In the first part of the study, two radiologists independently evaluated the visibility of first-, second-, and third-order branch arteries in the neck. In the second part of the study, the number of feeding arteries for every paraganglioma was determined and compared with digital subtraction angiography (DSA), the standard of reference in this study. RESULTS: Three-dimensional TOF angiography was superior to the other MR angiography techniques studied (P < .05) for depicting branch arteries of the external carotid artery in the neck, but only first- and second-order vessels were reliably shown. DSA showed a total of 78 feeding arteries in the group of patients with 29 paragangliomas, which was superior to what was revealed by all MR angiography techniques studied. More tumor feeders were identified with 3D TOF and 2D TOF angiography than with 3D PC MR angiography (P < .05), with a sensitivity/specificity of 61%/98%, 54%/95%, and 31%/95%, respectively. Sensitivity was lowest for carotid body tumors. CONCLUSION: Compared with intra-arterial DSA, the 3D TOF MR angiography technique was superior to 3D PC and 2D TOF MR angiography for identifying the first- and second-order vessels in the neck. With 3D TOF angiography, more tumor feeders were identified than with the other MR angiography techniques studied. The sensitivity of MR angiography, however, is not high enough to reveal important vascularization. The sensitivity of MR angiography is too low to replace DSA, especially in the presence of carotid body tumors.

Acromegaly: report of two patients with an unusual presentation.

The presenting features of functionally active pituitary tumours depend on the specific hormone which is overproduced. Growth hormone (GH) producing tumours usually present with the clinical manifestations of acromegaly due to excessive GH secretion or symptoms resulting from mass effects of the enlarging tumour. The changes in physical features and the increase in tumour size are usually insidiously slow and therefore, recognition of the disease is delayed. In this report two patients with acromegaly are described with an atypical presentation due to acute onset of symptoms. The first patient presented with central diabetes insipidus. The diagnosis acromegaly was made on physical examination. The second patient presented with a generalized seizure during sleep. On CT-scanning a large tumour protruding into the left temporal lobe connected to the pituitary gland was seen. Immunohistochemistry of the tumour after partial transcranial resection confirmed the clinical diagnosis of acromegaly. At a later stage transsphenoidal resection of the pituitary tumour was performed with full recovery and without loss of pituitary function.

Color Doppler imaging of paragangliomas in the neck.

PURPOSE: In this study, we describe the color Doppler imaging findings in carotid body tumors and vagal body tumors. METHODS: B-mode and color Doppler imaging were performed on 17 patients who had a total of 25 previously diagnosed paragangliomas (14 carotid body tumors and 11 vagal body tumors). RESULTS: Nineteen of 25 tumors were depicted. Five small vagal body tumors in the region of the nodose ganglion and 1 carotid body tumor could not be depicted. With B-mode imaging, paragangliomas appeared as well-defined, solid, hypoechoic masses. With color Doppler imaging, hypervascularity with a low-resistance flow pattern was demonstrated in all but 1 of the 19 tumors. CONCLUSIONS: The use of color Doppler imaging in the workup of an ambiguous neck mass is advocated.

Carcinoid tumor of the jugulo-tympanic region.

Increased levels of 5-hydroxyindole acetic acid (5-HIAA) were found in a patient with a tumor arising in the middle ear. Iodine-123-metaiodobenzylguanidine ([123I]MIBG) scintigraphy and biochemical analysis showed evidence of serotonin production by the tumor. Immunohistochemistry of the tumor showed reactivity with antibodies directed against serotonin, chromogranin, leu-7 and neuron-specific enolase; S-100, met-enkephalin, leu-enkephalin and glial fibrillary acid protein were negative. This case suggests a close relationship between functioning paragangliomas and carcinoid tumors because a strong clinical and endocrinological resemblance exists. The hormonal activity found is discussed in relation to extra-adrenal paragangliomas. We recommend urinary screening not only for detection of increased levels of catecholamines, but also of 5-HIAA in all patients with paragangliomas of the head and neck. When elevated levels are found, [123I]MIBG scintigraphy should be performed to localize the areas of increased uptake in or outside the head and neck region.

From medical history and biochemical tests to presymptomatic treatment in a large MEN 2A family.

An extensive study was published in 1959 in the Netherlands on a large family, which initially attracted attention because of a family history of attacks of shaking. Clinical investigation revealed phaeochromocytomas in four family members. In 1975, the family was identified to be a MEN 2A family, and since then, the members were examined annually using measurement of catecholamine metabolites in 24-h excreted urine and C-cell stimulation tests. In 1993, the RET proto-oncogene on chromosome 10q11 was found to be associated with MEN 2A and a specific mutation in this gene was identified in the family. In this family, 32 MEN 2A patients were detected. Since screening started in 1975, no patient died of phaeochromocytoma; however, two patients died of metastasized medullary thyroid carcinoma (MTC) (mean age 46 years). Twelve patients were operated on for phaeochromocytoma, and 13 for MTC. The results of DNA-analysis revealed the failures of the biochemical tests to identify affected family members. Six disease gene carriers with normal C-cell stimulation test results appeared to have small multifocal MTCs. Two carriers with normal excretion levels of catecholamines had a small phaeochromocytoma. DNA-analysis enables the unambiguous diagnosis of MEN 2A gene carrier-ship, allowing presymptomatic surgery for MTC.

Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A.

BACKGROUND: Multiple endocrine neoplasia type 2A (MEN-2A) is characterized by medullary thyroid carcinoma in combination with pheochromocytoma and sometimes parathyroid adenoma. Missense mutations in the RET proto-oncogene are associated with MEN-2A. Their detection by DNA analysis allows the identification of carriers of the gene, in whom the risk of medullary thyroid carcinoma is 100 percent. We compared the reliability of biochemical tests with that of DNA analysis in identifying carriers of the MEN2A gene. METHODS: Starting in 1975, we screened 300 subjects in four large families with MEN-2A for expression of the disease, using measurements of plasma calcitonin after stimulation with pentagastrin or calcium and urinary excretion of catecholamines and catecholamine metabolites. We tested for carrier status by DNA analysis, including linkage analysis, and more recently by analysis of mutations in the RET gene. RESULTS: Of 80 MEN2A gene carriers (in 61 of whom carrier status was proved by DNA analysis), 66 had abnormal plasma calcitonin values and medullary thyroid carcinoma. Fourteen young carriers had normal results of plasma calcitonin tests. In 8 of these 14, thyroidectomy revealed small foci of medullary thyroid carcinoma; the remaining 6 have not yet been operated on. Of the other 220 family members, 68 were found by DNA analysis not to carry the MEN2A gene. None of these 68 subjects had medullary thyroid carcinoma or pheochromocytoma; 6 had elevated plasma calcitonin concentrations and underwent thyroidectomy but had only C-cell hyperplasia. CONCLUSIONS: Unlike biochemical tests, DNA analysis permits the unambiguous identification of MEN2A gene carriers.

Von Hippel-Lindau disease: new strategies in early detection and treatment.

UNLABELLED: Von Hippel-Lindau disease is an autosomal dominant inherited disorder causing hemangioblastomas of the central nervous system (CNS), retinal hemangiomas, renal cell carcinomas, pheochromocytomas, pancreatic and liver cysts, and epididymal cystadenomas. PURPOSE: Since 1976, we have periodically screened for the lesions in a large affected family and were able to evaluate new strategies in detection and treatment. PATIENTS AND METHODS: A total of 23 individuals underwent the screening program. A multidisciplinary team of physicians was involved. RESULTS: In 13 patients (7 females and 6 males), a total of 31 tumors was detected; hemangioblastoma of the CNS (9), retinal angioma (4), renal involvement (8), pheochromocytoma (4), pancreatic lesions (4), and liver lesions (2) were diagnosed by periodic family screening. On the basis of more than 10 years of experience and current literature, new criteria for diagnosis and treatment have been proposed. CONCLUSION: The von Hippel-Lindau disease gene appears to be a tumor suppressor gene, and its absence or a defect in its structure is responsible for the predisposition to the disease. Tumor development depends on a somatic second mutation in the homologous allele. That means, in disease-gene carriers, tumor growth may begin at any age. Most of the lesions can be treated successfully when diagnosed in time. Periodic screening by a multidisciplinary team has to be continued lifelong.

CT and MR distinction of adenomas and nonadenomas of the adrenal gland.

OBJECTIVE: Because the distinction between adenomas and nonadenomas of the adrenal gland is essential, we investigated which of the following parameters--size, CT attenuation values, MRI signal intensity ratios on T1- and T2-weighted sequences, calculated T2 relaxation times, or T2 relaxation time ratios--provides better discrimination. MATERIALS AND METHODS: We compared these parameters in 44 adrenal masses of 37 patients by means of the Student t test and receiver operating characteristics (ROC) analyses. RESULTS: Only size, CT attenuation values, and signal intensity ratios on T2-weighted MR images of adenomas showed a significant difference from those of nonadenomas. With use of ROC analysis, CT demonstrated a significantly larger area under the curve compared to size and T2 signal intensity ratios, indicating superior performance. CONCLUSION: We found attenuation values on non-contrast-enhanced CT to be the best method in discriminating adrenal adenomas from nonadenomas. Adrenal masses with CT attenuation values below 15 HU warrant no further investigations.

Magnetic resonance imaging or metaiodobenzylguanidine scintigraphy for the demonstration of paragangliomas? Correlations and disparities.

Paragangliomas are tumours arising from paraganglionic tissue dispersed from the base of the skull to the pelvic diaphragm. These tumours produce symptoms by secreting catecholamines (functioning tumours) or by local tumour expansion. They can be part of several hereditary disorders. The introduction of magnetic resonance (MR) imaging and metaiodobenzylguanidine (MIBG) scintigraphy has provided new insights into paragangliomas and has tremendously changed the topographic diagnosis of paragangliomas. Both techniques have proven to be adequate in localising paragangliomas. In this report, the performance of these two noninvasive imaging methods in the examination of paragangliomas is compared and the merits and deficits of the two techniques are discussed. Both techniques produce comparable results in the detection of functioning paragangliomas. MR imaging, however, also demonstrates tumours that do not take up MIBG. MR imaging does not involve the use of ionising radiation and is not hampered by medication. Moreover, MR imaging has a higher spatial resolution. Because of these merits it is concluded that for demonstration of paragangliomas, whole-body MR imaging is the preferred and initial method of investigation. MIBG scintigraphy, on the other hand, continues to be a reliable method for non-invasive detection of functioning paragangliomas. At present it is clearly faster in whole-body imaging than MRI and it is definitely patient-friendly (no claustrophobia). It could be reserved for cases where a strong suspicion of a functioning paraganglioma persists, despite normal MR imaging findings, and for cases where doubt exists about the functional activity of one or more multicentric tumours. MIBG scintigraphy must be used in the evaluation of patients referred for iodine-131 MIBG treatment.

MR diagnosis of paraganglioma of the head and neck: value of contrast enhancement.

OBJECTIVE: Contrast enhancement with gadopentetate dimeglumine has been advocated to increase the efficacy of MR imaging for paragangliomas of the head and neck. However, contrast media are expensive, time-consuming to use, and involve minimal but not negligible risks. The purpose of this study was to determine if the use of contrast material is warranted in patients undergoing MR imaging for the diagnosis of paragangliomas of the head and neck. MATERIALS AND METHODS: Unenhanced MR images were compared with images obtained after administration of gadopentetate dimeglumine in 23 healthy subjects and 37 patients who had a total of 71 tumors. Three combinations of sequences were reviewed independently and in a random order by four observers who had no clinical information. Combination A comprised enhanced and unenhanced T1-weighted sequences, combination B comprised unenhanced T1- and T2-weighted sequences, and combination C was a combination of all sequences. A four-point scale of certainty was used. CT, scintigraphic, angiographic, and surgicopathologic findings were used as the standard of reference. Results were subjected to alternative free-response receiver-operating-characteristic (AFROC) scoring and statistical analysis. RESULTS: The mean areas under the AFROC curve for combinations A, B, and C were 0.761, 0.856, and 0.827, respectively. Mean sensitivity/specificity values after dichotomizing the scoring results were 0.73/0.94, 0.79/0.95, and 0.78/0.94 for combinations A, B, and C, respectively. The performance of combinations B and C did not differ markedly, but both combinations were significantly better than combination A. In a relatively large percentage (36%) of small postoperative tumor residues not detected on unenhanced images, however, gadopentetate dimeglumine allowed detection. CONCLUSION: The results of this study indicate that, in general, the use of gadopentetate dimeglumine is not necessary for the detection of head and neck paragangliomas. The addition of contrast-enhanced imaging does not increase the sensitivity or specificity compared with imaging without enhancement. Only when searching for small postoperative tumor residues is the addition of gadopentetate dimeglumine warranted.

Carotid bifurcation imaging: magnetic resonance angiography compared to conventional angiography and Doppler ultrasound.

PURPOSE: to evaluate the clinical usefulness of the two dimensional "Time of Flight" (2D TOF) Magnetic Resonance Angiography technique (MRA) in imaging the carotid bifurcation as compared to conventional angiography and pulsed and colour Doppler ultrasound. METHODS: in 19 patients with possible cerebrovascular disease and eight volunteers, contrast angiography was compared with MRA in 21 carotid bifurcations and with Doppler ultrasound in 23 bifurcations by two independent observers. In 19 bifurcations, all three techniques were available for comparison. Internal carotid arteries were graded normal/minimal disease, mild, moderate or severe stenosis, or occluded. RESULTS: overall agreement between contrast angiography and MRA existed in 62% for one observer and 76% for the other. When MRA and Doppler agreed, agreement between these two investigations and contrast angiography existed in 77-81%. The major problem with MRA was overestimation of moderately stenosed vessels; 50% of the vessels with a moderate stenosis on contrast angiography were judged severely stenosed on MRA. An occlusion was never mistaken for a stenosis by MRA. Evaluating the separate slices, acquired in the 2D TOF MRA investigation, appeared to be essential to avoid this mistake. CONCLUSION: at present 2D TOF MRA is not clinically useful for diagnosing the degree of carotid artery stenosis. MRA has a clear tendency to overestimate the degree of stenosis especially moderately severe stenoses. To date, there are no objective methods to correct for this mistake. Technical improvements may make MRA a better diagnostic tool in the future.

MRI screening of kindred at risk of developing paragangliomas: support for genomic imprinting in hereditary glomus tumours.

Paragangliomas of the head and neck (glomus tumours) can occur in a hereditary pattern and may be hormonally active as well as being associated with paragangliomas elsewhere. A number of these tumours may be present without symptoms. To detect the presence of subclinical paragangliomas we screened 83 members of a family at risk of developing hereditary paragangliomas using whole body MRI and urinary catecholamine testing. In eight previously diagnosed members, eight known glomus tumours of which one functioning, and two unknown glomus tumours and one unknown pheochromocytoma were present. Six unsuspected members showed ten glomus tumours and one pheochromocytoma. It has been suggested that the manifestation of hereditary glomus tumours is determined by the sex of the transmitting parent. There were no tumours in the descendants of female gene carriers. Comparing the likelihood of inheritance with genomic imprinting versus inheritance without genomic imprinting we found an odds ratio of 23375 in favour of genomic imprinting.

A gene subject to genomic imprinting and responsible for hereditary paragangliomas maps to chromosome 11q23-qter.

Paragangliomas of the head and neck are slow growing tumors which rarely show malignant progression. Familial transmission has been described consistent with an autosomal dominant mode of inheritance. Clinical manifestations of hereditary paragangliomas are determined by the sex of the transmitting parent. All affected individuals have inherited the disease gene from their father, expression of the phenotype is not observed in the offspring of an affected female until subsequent transmittance of the gene through a male carrier. This finding strongly suggests that genomic imprinting is involved. We report the results of a linkage study on a large Dutch pedigree with hereditary paragangliomas. Highly significant evidence for genetic linkage to chromosome 11q23-qter with the anonymous DNA marker D11S147 was detected with a peak lod score of 6.0 at a recombination fraction theta = 0.0. Likelihood calculations yielded an odds ratio of 2.7 x 10(6) in favor of genomic imprinting versus the absence of genomic imprinting.

MR imaging and MIBG scintigraphy of pheochromocytomas and extraadrenal functioning paragangliomas.

To compare the potential of magnetic resonance (MR) imaging and scintigraphy performed with radiotracer-labeled metaiodobenzyl-guanidine (MIBG) in localization and characterization of functioning paragangliomas, the authors analyzed results of both modalities in 33 patients. Overall sensitivity for detection was 91% for MR imaging and 80% for MIBG scintigraphy. MR imaging demonstrated 100% of adrenal paragangliomas and 75% of extraadrenal paragangliomas, whereas MIBG scintigraphy revealed 75% and 88%, respectively. MIBG scintigraphy was more specific in the characterization of paragangliomas than MR imaging (100% vs 82%). However, MR imaging demonstrated nine other lesions not seen on scintigrams. On the basis of their results and other considerations, the authors believe MR imaging is the preferred initial technique when a functioning paraganglioma is suspected.

Iodine-123-metaiodobenzylguanidine scintigraphy in patients with chemodectomas of the head and neck region.

While studying the uptake of iodine-123-metaiodobenzylguanidine ([123I]MIBG) in chemodectomas, we coincidentally detected catecholamine secreting tumors in 5 out of 14 patients. In three of these cases, a norepinephrine secreting abdominal paraganglioma was subsequently removed. One patient had a norepinephrine secreting chemodectoma and one had a dopamine secreting chemodectoma. Prior to [123I]MIBG imaging and urinary catecholamine measurements, endocrine activity was suspected in only one of these five patients. Apart from these five cases, two other patients showed elevated catecholamine secretion and abnormal abdominal [123I]MIBG concentrations. However, these two patients were not surgically explored, because of normal computed tomography (CT) and magnetic resonance (MRI) studies. We suspect that catecholamine-secreting tumors are more common in patients with chemodectomas than is assumed in the literature, and we therefore recommend urinary catecholamine screening for all patients with chemodectomas. In case of elevated catecholamine secretion, MIBG scintigraphy is indicated.