Multiphasic MR imaging: a new method for direct imaging of pulsatile CSF flow

A new technique is described that allows for the creation of pure pulsatile flow magnetic resonance (MR) images in a single acquisition. Five to 16 electrocardiographically gated images spanning the entire cardiac cycle are obtained with use of a gradient-echo pulse sequence. The section can be varied from 4 mm thick to full thickness projection. Taken singly, each image provides direct assessment of flow direction and velocity. Subtraction of image pairs eliminates signal detected from stationary protons, producing images of pulsatile flow. In this study the technique was used to image the flow of cerebrospinal fluid (CSF) in healthy subjects and in one patient with syringohydromyelia. The data suggest that multiphasic MR imaging provides a powerful means for the noninvasive assessment of CSF pulsatile flow dynamics and may have potential clinical application for the investigation of a variety of abnormalities such as normal pressure hydrocephalus, syrinx, and spinal block.     

MR gated subtraction angiography: evaluation of lower extremities

We report the first clinical experience with a new method for projective imaging of blood vessels (angiography) using magnetic resonance. Vascular contrast is produced noninvasively by the phase response of moving protons. Diastolic and systolic gated images produce, respectively, flow signal and flow void; the difference image is a map of the pulsatile flow: an arteriogram. Preliminary studies are presented of the lower extremities of one healthy volunteer and four patients (one each with occlusive disease, soft-tissue tumor, arteriovenous malformation, and venous femoral-popliteal graft). Patient data are compared with accompanying conventional arteriograms, and the new method is discussed.     

Quantification of blood flow with dynamic MR imaging and presaturation bolus tracking

A technique is described for rapid imaging of blood flow and dynamic measurement of its velocity. The method is a combination of bolus tracking and low-flip-angle gradient-echo cine angiography. This method provides precise determination of velocity with high temporal resolution in a single measurement. Unlike what occurs in phase imaging techniques, flow is displayed directly, eliminating potential errors that result from non-flow-related sources of phase shifts. Manipulation of raw data sets is avoided. Results obtained from a flow phantom, healthy volunteers, and a patient with an aortic aneurysm demonstrate the capability of the technique to track flow at low and high velocities and to differentiate flowing blood from thrombus. Because of its conceptual simplicity, rapidity, and lack of susceptibility to extraneous phase shifts, this technique may prove ideal for in vivo flow measurement and evaluation of flow patterns.     

A comparison between activated protein C and des-1-41-light chain- activated protein C in reactions with type 1 plasminogen activator inhibitor

This study investigates the role of the gamma-carboxyglutamic acid (gla) containing domain of activated protein C in interactions with both platelet-derived and purified type 1 plasminogen activator inhibitor (PAI-1). The activity of human platelet PAI-1 was neutralized to the same extent by bovine activated protein C and bovine des-1-41- light chain-activated protein C. Both forms of activated protein C formed SDS-stable, divalent-cation independent complexes with platelet PAI-1, as demonstrated by immunoblotting using antibodies directed to either protein C or PAI-1. Since activated protein C neutralized PAI-1, the potential inhibition of the enzyme by PAI-1 was studied. Purified PAI-1 inhibited the amidolytic activity of bovine-activated protein C and bovine des-1-41-light chain-activated protein C with a k2 of 2.85 X 10(4) M-1 sec-1 for both proteins. These data suggest that the gla domain of activated protein C is not required for neutralization of PAI- 1 activity, for complex formation with PAI-1, or for inhibition of the amidolytic activity of activated protein C by PAI-1.     

The treatment of malignant histiocytosis

Twenty-four consecutive cases of malignant histiocytosis (MH) treated at Stanford Medical Center between 1973 and 1983 have been reviewed. Most patients presented with systemic symptoms (91%) and advanced disease (stage IV, 80%). Multiple organ involvement was common. In six cases, pathologic tissue was further characterized by frozen section immune histochemistry, using a panel of monoclonal antibodies known to react with monocytes and macrophages, as well as a variety of hematopoietic cells. One case expressed a mature monocyte/macrophage phenotype; three cases were considered null cell or primitive lesions; and two cases were identified as probable T cell lymphomas. Seven patients underwent splenectomy. Two patients died prior to any treatment. Twenty-two patients were treated with CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone) +/- bleomycin (B), +/- midcycle high-dose methotrexate (HD-MTX) with leucovorin rescue. Seven patients received prophylactic intrathecal MTX. Of 22 evaluable patients, there was a 68% complete response rate (CR), a 23% partial response rate (PR), and a 9% no response rate (NR). Median duration of CR was 30+ months; median duration of PR was 2.4 months. Median survival for patients attaining a CR has not been reached v 3 months for the PR and NR groups. For all 24 patients, median survival was 2 years, with a 5-year actuarial survival of 40%. Multivariate analysis revealed that a platelet count less than 150,000 (P Cox = .005) and the dose of drug delivered (P Cox = .057) were the most important prognostic factors. Prophylactic intrathecal MTX therapy and splenectomy did not influence survival. Although MH is an aggressive disease with a poor prognosis, it is potentially curable. Systematic and aggressive treatment should further improve the outcome.     

Paediatric nodal marginal zone B‐cell lymphadenopathy of the neck: a Haemophilus influenzae‐driven immune disorder?

Many hyperplasias and lymphomas of marginal zone B‐cells are associated with infection. We identified six children and one adolescent with cervical lymphadenopathy showing prominent polyclonal nodal marginal zone hyperplasia (pNMZH) and four adolescents with monoclonal paediatric nodal marginal zone lymphoma (pNMZL). The clonality status was assessed using BIOMED‐2‐IG PCR analysis. Haemophilus influenzae was identified in all six cases of pNMZH that could be tested by direct culture (N = 3) or a very sensitive PCR for the H. influenzae gyrase gene in frozen materials (N = 5). H. influenzae was not detected in three pNMZLs and 28 non‐specific reactive cervical lymph nodes of age‐matched controls, except for a single control node that was obtained during oropharyngeal surgery for a cleft palate showing very low copy numbers of H. influenzae. pNMZH patients were younger than pNMZL patients (median age 12 versus 21 years). pNMZH showed a prominent nodular appearance with variable fibrosis without acute inflammation. Within the nodules, the expanded germinal centres and variably sized marginal zones were colonized by activated B‐cells with weak expression of IgD and lack of CD10 and/or BCL6 expression. Some areas showed skewed light chain expression in plasma cells (4/5 cases lambda). In four cases tested, this was confirmed by flow cytometry for surface Ig (3/4 cases lambda). In contrast, pNMZL showed more extensive expansion of marginal zones by centrocytoid cells and often expression of BCL2 protein. Several H. influenzae strains are known to interact with the constant part of IgD on human B‐cells, leading to their polyclonal proliferation and activation. We speculate that in vivo stimulation of IgD+ marginal zone B‐cells by this bacterium may be implicated in this particular lymphadenopathy that should be distinguished from monoclonal pNMZL. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.