Navigated laparoscopic microwave ablation of tumour mimics in pig livers: a randomized ex-vivo experimental trial.

BACKGROUND: In order to efficiently perform laparoscopic microwave ablation of liver tumours precise positioning of the ablation probe is mandatory. This study evaluates the precision and ablation accuracy using the innovative laparoscopic stereotactic navigation system CAS-One-SPOT in comparison to 2d ultrasound guided laparoscopic ablation procedures. METHODS: In a pig liver ablation model four surgeons, experienced (n = 2) and inexperienced (n = 2) in laparoscopic ablation procedures, were randomized for 2d ultrasound guided laparoscopic or stereotactic navigated laparoscopic ablation procedures. Each surgeon performed a total of 20 ablations. Total attempts of needle placements, time from tumor localization till beginning of ablation and ablation accuracy were analyzed. RESULTS: The use of the laparoscopic stereotactic navigation system led to a significant reduction in total attempts of needle placement. The experienced group of surgeons reduced the mean number of attempts from 2.75 ± 2.291 in the 2d ultrasound guided ablation group to 1.45 ± 1.191 (p = 0.0302) attempts in the stereotactic navigation group. Comparable results could be observed in the inexperienced group with a reduction of 2.5 ± 1.50 to 1.15 ± 0.489 (p = 0.0005). This was accompanied by a significant time saving from 101.3 ± 112.1 s to 48.75 ± 27.76 s (p = 0.0491) in the experienced and 165.5 ± 98.9 s to 66.75 ± 21.96 s (p < 0.0001) in the inexperienced surgeon group. The accuracy of the ablation process was hereby not impaired as postinterventional sectioning of the ablation zone revealed. CONCLUSION: The use of a stereotactic navigation system for laparoscopic microwave ablation procedures of liver tumors significantly reduces the attempts and time of predicted correct needle placement for novices and experienced surgeons without impairing the accuracy of the ablation procedure.

Changes in stiffness and biochemical composition of the pericellular matrix as a function of spatial chondrocyte organisation in osteoarthritic cartilage.

OBJECTIVE: During osteoarthritis (OA), chondrocytes seem to change their spatial arrangement from single to double strings, small and big clusters. Since the pericellular matrix (PCM) appears to degrade alongside this reorganisation, it has been suggested that spatial patterns act as an image-based biomarker for OA. The aim of this study was to establish the functional relevance of spatial organisation in articular cartilage. METHOD: Cartilage samples were selected according to their predominant spatial cellular pattern. Young's modulus of their PCM was measured by atomic force microscopy (AFM) (∼500 measurements/pattern). The distribution of two major PCM components (collagen type VI and perlecan) was analysed by immunohistochemistry (8 patients) and protein content quantified by enzyme-linked immunosorbent assay (ELISA) (58 patients). RESULTS: PCM stiffness significantly decreased with the development from single to double strings (p = 0.030), from double strings to small clusters (p = 0.015), and from small clusters to big clusters (p < 0.001). At the same time, the initially compact collagen type VI and perlecan staining progressively weakened and was less focalised. The earliest point with a significant reduction in protein content as shown by ELISA was the transition from single strings to small clusters for collagen type VI (p = 0.016) and from double strings to small clusters for perlecan (p = 0.008), with the lowest amounts for both proteins seen in big clusters. CONCLUSIONS: This study demonstrates the functional relevance of spatial chondrocyte organisation as an image-based biomarker. At the transition from single to double strings PCM stiffness decreases, followed by protein degradation from double strings to small clusters.

Medical students' attitude towards artificial intelligence: a multicentre survey.

OBJECTIVES: To assess undergraduate medical students' attitudes towards artificial intelligence (AI) in radiology and medicine. MATERIALS AND METHODS: A web-based questionnaire was designed using SurveyMonkey, and was sent out to students at three major medical schools. It consisted of various sections aiming to evaluate the students' prior knowledge of AI in radiology and beyond, as well as their attitude towards AI in radiology specifically and in medicine in general. Respondents' anonymity was ensured. RESULTS: A total of 263 students (166 female, 94 male, median age 23 years) responded to the questionnaire. Around 52% were aware of the ongoing discussion about AI in radiology and 68% stated that they were unaware of the technologies involved. Respondents agreed that AI could potentially detect pathologies in radiological examinations (83%) but felt that AI would not be able to establish a definite diagnosis (56%). The majority agreed that AI will revolutionise and improve radiology (77% and 86%), while disagreeing with statements that human radiologists will be replaced (83%). Over two-thirds agreed on the need for AI to be included in medical training (71%). In sub-group analyses male and tech-savvy respondents were more confident on the benefits of AI and less fearful of these technologies. CONCLUSION: Contrary to anecdotes published in the media, undergraduate medical students do not worry that AI will replace human radiologists, and are aware of the potential applications and implications of AI on radiology and medicine. Radiology should take the lead in educating students about these emerging technologies. KEY POINTS: • Medical students are aware of the potential applications and implications of AI in radiology and medicine in general. • Medical students do not worry that the human radiologist or physician will be replaced. • Artificial intelligence should be included in medical training.

Prospective Analyses of Circulating B Cell Subsets in ABO-Compatible and ABO-Incompatible Kidney Transplant Recipients.

Immunosuppressive strategies applied in renal transplantation traditionally focus on T cell inhibition. B cells were mainly examined in the context of antibody-mediated rejection, whereas the impact of antibody-independent B cell functions has only recently entered the field of transplantation. Similar to T cells, distinct B cell subsets can enhance or inhibit immune responses. In this study, we prospectively analyzed the evolution of B cell subsets in the peripheral blood of AB0-compatible (n = 27) and AB0-incompatible (n = 10) renal transplant recipients. Activated B cells were transiently decreased and plasmablasts were permanently decreased in patients without signs of rejection throughout the first year. In patients with histologically confirmed renal allograft rejection, activated B cells and plasmablasts were significantly elevated on day 365. Rituximab treatment in AB0-incompatible patients resulted in long-lasting B cell depletion and in a naïve phenotype of repopulating B cells 1 year following transplantation. Acute allograft rejection was correlated with an increase of activated B cells and plasmablasts and with a significant reduction of regulatory B cell subsets. Our study demonstrates the remarkable effects of standard immunosuppression on circulating B cell subsets. Furthermore, the B cell compartment was significantly altered in rejecting patients. A specific targeting of deleterious B cell subsets could be of clinical benefit in renal transplantation.

Operating room time savings in Germany- and UK-based hospitals with 3D- VS. 2D-imaging technology in laparoscopic surgery: Meta analysis and budget impact model - Health economic evaluation.

AIMS: Opportunity cost (OC) analysis is key when evaluating surgical techniques. Operating room (OR) time is one potential source of OC in laparoscopic surgery. This study quantifies differences in OR time between 3D- and 2D-imaging technology in laparoscopic surgery, translates these into OC and models the economic impact in real-world hospitals. METHODS: First a systematically performed literature review and meta-analysis were conducted. Then, methods to translate OR time savings into OC were theorised and a budget impact model was created. After that, the potential time savings of real-world hospital case mixes were extrapolated. Finally, the opportunity costs of not using 3D-imaging in laparoscopic surgery were evaluated. RESULTS: Average OR time saving per laparoscopic procedure was -19.4 min (-24.3; -14.5) (-14%) in favour of 3D. The Budget Impact Model demonstrated an economic impact of using 3D-laparoscopy instead of 2D laparoscopy, ranging from £183,045-£866,316 in the British and 73,049€-437,829€ in German hospitals, modelling a mixture of cost savings and performing additional procedures (earning additional revenue). CONCLUSION: The OC analysis revealed significant economic benefits of introducing 3D-imaging technology in laparoscopic surgery, on the basis that average procedure time is reduced. Utilising the saved OR time to perform additional procedures was the biggest driver of OC. Hospital case mix and procedure volume indicated the magnitude of the OC.

Electro-physiological parameters of hepatic radiofrequency ablation--a comparison of an in vitro versus an in vivo porcine liver model.

BACKGROUND: Radiofrequency ablation (RFA) is an inherent part of curative treatment within a multimodal therapy concept of malignant liver tumors. The biggest problem is the high rate of local recurrences in tumors with a diameter of more than 3 cm because of the high variability and poor reproducibility of the zone of ablation. No imaging modality facilitates monitoring during neither intraoperativ nor percutaneous RFA. This experimental study describes and compares an in vitro and in vivo porcine model by its electro-physiological parameters with the aim of monitoring RFA procedures. MATERIALS AND METHODS: RFA was performed in a perfused in vitro porcine (one RFA per liver) and in vivo porcine model (24 animals) with three different RFA systems (Rita XL 5 cm, Rita XLi 7 cm, LeVeen 5 cm). In the in vivo model, percutaneous placement of the RFA device was guided by native and contrast-enhanced CT scan. The electro-physical parameters during RFA were online (in real time) recorded by a dedicated software. After the RFA, the livers were explanted, sliced, and measured according to the consensus technique. RESULTS: The delivered energy was in vivo versus in vitro: Rita XL 238 +/- 135 kJ versus 135 +/- 53 kJ (p = 0.247); Rita XLi 711 +/- 180 kJ versus 159 +/- 54 (p = 0.016) and with LeVeen 212 +/- 71 kJ (in vivo). The LeVeen system was inconsistent in the in vitro model. This correlates to an energy consumption per ml of necrosis in vivo versus in vitro Rita XL of 8 +/- 3 kJ/ml versus 6.4 +/- 3.9 kJ/ml (p = 0.537), Rita XLi of 10 +/- 6 kJ/ml versus 1.8 +/- 0.2 kJ/ml (p = 0.016), and LeVeen of 14.0 +/- 12 kJ/ml (in vivo). The volume of ablation was in vivo versus in vitro Rita XL 30 +/- 10 ml versus 26 +/- 17 ml (p = 0.329), Rita XLi 90 +/- 58 ml versus 88 +/- 21 ml (p = 0.905), and LeVeen 22 +/- 11 ml versus 50 +/- 12 ml (p = 0.04). The impedance during RFA were in vivo versus in vitro Rita XL 39 +/- 4 Omega versus 50 +/- 14 Omega (p < 0.247), Rita XLi 33 +/- 5 Omega versus 61 +/- 16 Omega (p = 0.016) and LeVeen 31 +/- 2 Omega (in vivo). CONCLUSION: The volume of ablation showed analogue data in vivo and in vitro. The delivered energy and energy consumption was in vivo up to five times (Rita XLi) higher than in vitro and the impedance in vivo was always lower than in vitro. These differences observed between in vivo and in vitro were more pronounced than previously described. Thus the use of an in vitro model for research of the RFA technique must be challenged. The large deployment of the Rita XLi was a problem for percutaneous positioning of the device without direct contact to liver surface or major vessels in 80-kg pigs and to a lesser extent in in vitro liver originating from 130- to 140-kg pigs. Modern RFA systems which generate large volume of tissue necrosis can therefore only be adequately tested in a porcine model with a liver weight of at least 1.5-2 kg. Alternatively, a bovine liver model (with a liver weight up to 10 kg) should be developed in the future.

Postoperative Continuous Infusion of Local Anesthesia in Hand-Assisted Retroperitoneoscopic Living Donor Nephrectomy.

INTRODUCTION: Postoperative pain management in living kidney donor nephrectomy plays a key role in donor comfort and is important for the further acceptance of living kidney donation in times of organ shortage. Standard pain treatment (SPT) based on opioids is limited due to related side effects. Continuous infusion of local anesthesia (CILA) into the operative field is a promising alternative. The aim of this study was to evaluate whether CILA could reduce the dose of opioids in living kidney donors operated with hand-assisted retroperitoneoscopic donor nephrectomy (HARP). METHODS: An observational study on 30 living donors was performed. The primary outcome was the difference of morphine equivalents (MEQ) administered between CILA and SPT. RESULTS: On day 0 and 1, living donors with CILA received significant less MEQ compared to the SPT group, although on day 1 this effect was not statistically significant (day 0: 6.3 mg, interquartile range [IR] 4.2-11.2 vs 16.8 mg, IR 10.5-22.1, P = .009; day 1: 5.25 mg, IR 2.1-13.3 vs 13.3 mg, IR 6.7-23.8, P = .150). On days 2 and 3 there was no difference (day 2: 13.3 mg, IR 0.0-20.0 vs 13.3 mg, IR 6.7-13.3, P = .708; day 3: 13.3 mg, IR 0.0-26.7 vs 13.3 mg, IR 6.7-20, P = .825). Overall (days 0 to3) MEQ was also less for CILA without reaching statistical significance (39.6 mg, IR 10.9-70.5 vs 59.6 mg, IR 42.4-72.9, P = .187). CONCLUSIONS: CILA seems to be an effective instrument for donor pain management in the first 24 hours after HARP. Its effect abates by 48 hours after surgery, especially if highly potent nonopioids are given.

Laser angioplasty with a contact probe for the treatment of peripheral vascular disease.

Percutaneous transluminal laser angioplasty was carried out for the dilatation of 30 completely occluded peripheral arterial segments and three subtotal stenoses. A neodymium-YAG laser and an optical fibre delivery system with a sapphire tip were used. All three arterial stenoses and 26 of the 30 occluded arterial segments were successfully dilated. In 20 patients additional dilatation was carried out with a balloon catheter. Laser angioplasty failed to recanalise four occlusions, and vessel leakage without clinical consequences occurred in one patient. Reocclusion occurred within 48 h in two patients and after five months in one patient during a follow up period of at least six months. It is concluded that percutaneous transluminal laser angioplasty using direct contact with a sapphire tip is highly effective (89% success rate) in reopening peripheral vascular occlusions. The procedure is safe, and reocclusion of vessels is rare during the six month follow up period.

Plasma levels of parathyroid hormone-related peptide are elevated in hyperprolactinemia and correlated to bone density status.

Osteopenia is an important clinical manifestation of hyperprolactinemia. Bone loss in these patients has mainly been attributed to concomitant deficiency of gonadal hormones rather than to hyperprolactinemia per se. Parathyroid hormone-related peptide (PTHrP) is expressed in human mammary tissue, and elevated circulating PTHrP levels as well as concomitant hypercalcemia have been described during lactation. We sought to determine circulating PTHrP levels in patients with long-standing hyperprolactinemia and whether PTHrP may exert possible systemic effects on bone and mineral metabolism. We studied 45 patients (30 women and 15 men) with persisting hyperprolactinemia 6 +/- 4 years (mean +/- SD) after trans-sphenoidal surgery for prolactin-producing pituitary adenomas. PTHrP levels in 117 healthy controls were 10.6 +/- 7.3 pmol-eq/l (mean +/- SD). In hyperprolactinemic patients, plasma PTHrP was elevated to 30.3 +/- 13.4 pmol-eq/l (p < 0.001, n = 45), and in patients with humoral hypercalcemia of malignancy PTHrP levels were 52.9 +/- 29.6 (p < 0.001 to controls and hyperprolactinemic patients). Fifty-three percent of hyperprolactinemic patients (n = 24) had clearly elevated PTHrP levels (> 2 SD). Retrospective immunocytochemical studies of the removed pituitary adenomas from 19 patients generally showed a higher degree of immunoreactivity for PTHrP (1-34) in all but one case when compared with normal pituitary tissue. Patients with elevated circulating PTHrP levels showed in most instances strong immunoreactivity to PTHrP in 70-100% of tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain neurotransmitter changes in three patients who had a fatal hyperthermia syndrome.

The authors examined the autopsied brains from three patients who had a fatal hyperthermia syndrome. There was marked hypothalamic noradrenaline depletion in all three patients, severe brain choline acetyltransferase deficiency with nucleus basalis cell loss in two patients, and mild to moderate brain choline acetyltransferase loss in one patient. Striatal dopamine metabolite/dopamine ratio was below normal in two patients and not elevated, as would be expected after short-term neuroleptic administration, in the third. This suggests that reduced capability (aggravated by the cholinergic deficit) of the nigrostriatal dopamine system to respond adequately to stress and/or neuroleptic-induced receptor blockade may be important in the development and course of fatal hyperthermia syndrome.

Pathologic correlates of incidental MRI white matter signal hyperintensities.

We related the histopathologic changes associated with incidental white matter signal hyperintensities on MRIs from 11 elderly patients (age range, 52 to 82 years) to a descriptive classification for such abnormalities. Punctate, early confluent, and confluent white matter hyperintensities corresponded to increasing severity of ischemic tissue damage, ranging from mild perivascular alterations to large areas with variable loss of fibers, multiple small cavitations, and marked arteriolosclerosis. Microcystic infarcts and patchy rarefaction of myelin were also characteristic for irregular periventricular high signal intensity. Hyperintense periventricular caps and a smooth halo, however, were of nonischemic origin and constituted areas of demyelination associated with subependymal gliosis and discontinuity of the ependymal lining. Based on these findings, our classification appears to reflect both the different etiologies and severities of incidental MRI signal abnormalities, if it is modified to treat irregular periventricular and confluent deep white matter hyperintensities together.

Tumor cell markers in uveal melanoma.

Monoclonal antibodies to the melanoma-associated antigens HMB-45 and NKI/C3, and for S-100 protein were applied to archival tissue of 43 intraocular melanomas. Tn addition, the expression of the oncoproteins ras-p21 (ras 10) and mutated Ha-ras (E 184) as well as neu/erb-B2 (p185) were immunohistochemically evaluated. Incubation with antibodies to HMB-45 and NKI/C3 revealed consistently moderate to strong staining in all cases. Comparable ras-p21 immunostaining with normal epithelium observed in infiltrating components with a pronounced heterogeneous pattern, was particulary evident in epitheloid tumor cells. In melanomas of the spindle cell type B there was a tendency for patients with neu/erb-B2 positivity to have a worse prognosis. Using the chi-squared test for trend a significant correlation was found between S-100 reactivity, neu/erb-B2 amplification and the clinical outcome.

Lansoprazole versus famotidine: efficacy and tolerance in the acute management of duodenal ulceration.

Lansoprazole (AG 1749/CG 4801) is an inhibitor of gastric acid secretion by blocking H+,K(+)-ATPase. In this 2:1 randomized, double-blind, multicentre trial lansoprazole 30 mg am was compared to 40 mg famotidine nocte in 264 out-patients suffering from uncomplicated duodenal ulcer. After 2 weeks of treatment ulcer healing was confirmed endoscopically in a significantly higher proportion (P = 0.027) of patients treated with lansoprazole (94/174 = 54.0%) compared to patients receiving famotidine (35/90 = 38.9%). Cumulative healing rates after 4 weeks were 91.4% for the lansoprazole group and 83.3% for the famotidine group (P = 0.065). Pain relief and decrease of concomitant antacid consumption during treatment were comparable in both groups. Both compounds were well tolerated. Rates of recurrent duodenal ulcer in the 6 months after trial treatment were 45/158 (28.5%) after lansoprazole, and 18/69 (26.1%) after famotidine.

Dose-related healing of duodenal ulcer with the proton pump inhibitor lansoprazole.

Lansoprazole (AG 1749) is a novel substituted benzimidazole which inhibits gastric acid secretion by blocking H+,K(+)-ATPase. This randomized, double-blind multicentre trial studied the dose-response relationship of lansoprazole on ulcer healing and compared it with ranitidine in 314 out-patients with endoscopically assessed, symptomatic duodenal ulcer. Cumulative healing rates with Lansoprazole 7.5, 15, and 30 mg o.m. were 48, 59, and 74% at 2 weeks and 75, 84, and 95% at 4 weeks, respectively (intention-to-treat); the difference of the healing rates between 7.5 and 30 mg groups was significant (P less than 0.001). Corresponding healing rates for 300 mg ranitidine nocte were 51 and 89%. Pain relief was similar in all treatment groups. Lansoprazole was well tolerated. During a follow-up of 6 months relapse rates after lansoprazole 7.5, 15, and 30 mg were 21, 29, and 22%, respectively; the relapse rate after ranitidine 300 mg was 20%. In conclusion, lansoprazole provides faster healing of duodenal ulcer than ranitidine and a similar relapse pattern. For further trials in peptic ulcer disease a daily dose of lansoprazole 30 mg o.m. is recommended.

Contact probes for intravascular laser recanalization. Experimental evaluation.

Experimental laser ablation of atheromatous plaques was performed with a bare quartz glass fiber, a metal probe, and a sapphire probe. The tissue response after irradiation with increasing energies was evaluated by means of light and scanning electron microscopy. Laser emission through the bare fiber caused a narrow, deep crater with an irregular surface surrounded by a zone of thermal necrosis. After tissue ablation with the metal probe, a disproportion between the small tissue defect and the large zone of thermal necrosis was observed. The largest tissue defect was vaporized by the sapphire contact probe. A small zone of thermal necrosis surrounded the laser crater.

Non-invasive cardiac allograft monitoring: the graz experience.

Based on previous reports by our group, initial studies on non-invasive cardiac graft monitoring have been presented recently. In this study we define new parameters to monitor rejection and infection after heart transplantation (HTX) the ventricular evoked response (VER) T-slew rate parameter is defined as the maximum negative slope in the descending part of the repolarization phase of the VER. We calculated the VER duration parameter in milliseconds and defined it as the time between the pacemaker spike and the cross-over of the baseline, with the slope line used to calculate the VER T-slew rate. During the HTX procedure, we implant wide-band telemetric pacemakers and fractally coated, epimyocardial electrodes (Physios CTM 01 and ELC 54-UP, Biotronik; Berlin, Germany). During each follow-up and on biopsy days, intramyocardial electrogram sequences were obtained and sent via the Internet to the central data-processing unit in Graz. We scored the infection status of the patients before data acquisition. The VER parameters were automatically calculated and send back within a few minutes. We prospectivly compared 1,613 follow-ups from 42 patients with biopsy (International Society of Heart and Lung Transplantation grading) and infection classification. The VER duration parameter did not change during rejection; however, we found an increase during clinically apparent infection. The VER T-slew rate parameter was lower during rejection grade 2 or higher, as well as during clinically apparent infection. The negative predictive value to rule out rejection was 99%. Our results indicate that rejection and infection cause different, reproducible effects on the electrical activity of the transplanted heart. Non-invasive cardiac graft monitoring may reduce the need for surveillance biopsies and may offer a tool to optimize immunosuppressive therapy after HTX.

Prostaglandin E1 reduces the frequency of rejection after heart transplantation.

This retrospective study was carried out to evaluate the effect of prostaglandin E1 on the frequency of rejection in 36 heart transplant recipients who survived orthotopic heart transplantation for 60 days or longer. The therapy for both groups was the same except group 1 (n = 12) was given PGE1 for 6 to 14 days. Indication for the PGE1 was right ventricular mismatch or failure. The prostaglandin administration started during the transplantation procedure. The dosage was 28 to 64 ng/kg/min and was tapered down from 14.7 to 32 ng later. No major side effects related to PGE1 have been observed. During the first 60 days after heart transplantation, in the group treated with prostaglandin, rejection grade 2 or higher was evident in 0.91 biopsies/patient versus 2.2 in nontreated patients, (p less than 0.05). A prolonged interval free from rejection (p less than 0.05) was observed in the patients treated with prostaglandin.

Paced epimyocardial electrograms for noninvasive rejection monitoring after heart transplantation.

BACKGROUND: Diagnosis of acute heart rejection after transplantation with the help of epimyocardial electrograms has been reported as a sensitive and practicable method. Long-term follow-up has been limited, however, by variations o signal, which can be avoided by using pacemaker-induced signals. METHODS: For stimulation and detection of the ventricular evoked response, a new type of electrode with fractal surface structure was used. Seventeen patients undergoing heart transplantation were included in the study. Amplitudes of the depolarization and repolarization parts of ventricular evoked response signals were analyzed and related to the degree of acute rejection according to histologic findings from endomyocardial biopsy. RESULTS: In cases of focal moderate rejection (grade 2, International Society for Heart and Lung Transplantation grading) and higher degrees of rejection, significant amplitude decreases were found. CONCLUSION: This sensitive noninvasive method for rejection monitoring with a high level of reliability provides the possibility of reducing the number of endomyocardial biopsies.

MRI in tuberculous meningoencephalitis: report of four cases and review of the neuroimaging literature.

The contribution of MRI is reported in four adult patients with tuberculous meningoencephalitis (TbM) and with autopsy correlation in one. Contrast-enhanced T1-weighted MRI revealed the characteristic basal meningeal inflammation of TbM and its focal spreading into adjacent brain. Mixed and T2-weighted pulse sequences delineated a plethora of parenchymal abnormalities. Their relation to TbM was established by a close matching of the patient's neurological findings, contrast enhancement or a change in lesion size. The latter accurately reflected the clinical course in all patients. It remained difficult, however, to distinguish between ischaemic and inflammatory changes, which in some locations were intermixed even histologically. From our experience and that of other groups, MRI provides more diagnostic information in TbM than CT. Moreover, MRI promises to be a useful tool for monitoring treatment response.

The morphologic correlate of incidental punctate white matter hyperintensities on MR images.

Postmortem examinations were made of the brains of six patients, 52-63 years old, who exhibited incidental punctate white matter hyperintensities on MR images before death. Our aim was to unravel the morphologic correlate of such lesions. By repeating the MR study after fixation on four specimens, cutting the brain parallel to the MR imaging plane, and examining whole-hemisphere microscopic sections, we optimized lesion identification. The white matter signal abnormalities were better delineated on pre- than postmortem scans, and visual inspection of the brain slices was normal in all but one location. Histologically, we found areas of reduced myelination with atrophy of the neuropil around fibrohyalinotic arteries as well as different stages of perivenous damage. The latter ranged from spongiform transformation of the neuropil and scattered foci of demyelination to large perivenous areas with marked rarefaction of myelinated fibers. Edematous glial swelling in foci of ganglion cell heterotopia caused subcortical white matter hyperintensities in one case. Our results suggest minor perivascular damage but not infarction as the most likely substrate of punctate MR white matter hyperintensities in elderly brains. Histologic correlations with MR images obtained during life or with studies of unfixed material are necessary to analyze such small lesions.