Comparison between MRI-derived ADC maps and 18FLT-PET in pre-operative glioblastoma

Background and purposeAmong principal MRI sequences used for a better pre-therapeutic characterization of glioblastoma (GBM), DWI-derived ADC is expected to be a good parameter for the evaluation of cellularity, due to restricted water diffusivity. We aimed here to compare ADC maps to ¹⁸FLT-PET, a proliferation tracer, in GBM cases.Materials and methodsPatients underwent ¹⁸FLT-PET, followed by multiparametric magnetic resonance imaging (MRI) just prior to surgery. We analysed in this study twenty GBM confirmed patients. The 5th percentile (5p) of the ADC values were thresholded to define the ADC_min ROI, while the 95th percentile (95p) of the SUV FLT values were used to define the FLT_max ROI. The statistical and spatial correlations between these two groups of ROIs were analyzed.ResultsWe did not observe any significant correlations between ADC_min and FLT_max cut-off values (R² = 0.0285), neither between ADC_min and FLT_max ROIs (mean Dice = 0.09 ± 0.12). Mean ADC values in the FLT_max defined ROI were significantly higher than the values in the ADC_min ROI (P < 0.001). Mean FLT values in the FLT_max ROI were significantly higher than the values in the ADC_min ROI (P < 0.001).ConclusionsWhen comparing ADC maps to ¹⁸FLT uptake, we did not observe significant anatomical overlap nor correlation, between the regions of low ADC and high FLT disabling to clearly link ADC values to cellular proliferation. The exact significance of ADC maps in GBM has yet to be elaborated.     

Apparent diffusion coefficient histogram analysis for prediction of prognosis in glioblastoma

Background

To investigate the potential to predict prognosis of glioblastoma (GBM) patients by analysis of the broader and lower values in the lower distribution of apparent diffusion coefficient (ADC_L) (B&L-ADC_L) values in the ADC histogram.

ADC直方图在高级别胶质瘤与脑单发转移瘤鉴别中的应用价值

目的 探讨表观扩散系数（ADC）直方图鉴别高级别胶质瘤（HGG）与单发脑转移瘤（SBM）的价值。方法 回顾性分析病理或临床随访证实的7例HGG与19例SBM（腺癌脑转移瘤11例,鳞癌脑转移瘤8例）的MRI资料,测量瘤体和瘤周水肿区ADC直方图参数,利用受试者工作特征曲线评价ADC直方图参数鉴别HGG与SBM的诊断效能。结果 HGG瘤体ADC第5、25百分位数（ADC_5th、ADC_25th）及瘤周水肿ADC最小值（ADCmin）均明显低于SBM（P<0.05）,而瘤体体素计数明显高于SBM（P<0.05）。鳞癌脑转移瘤瘤体ADC_5th、ADC_25th均明显低于腺癌脑转移瘤（P<0.05）。瘤体ADC_5th=926×10-6 mm2/s鉴别诊断HGG与SBM的效能最高。结论 ADC直方图有助于HGG与SBM的鉴别诊断,瘤体ADC_5th鉴别诊断HGG与SBM的效能最高。     

Diffusion, perfusion, and T2 magnetic resonance imaging of anti-intercellular adhesion molecule 1 antibody treatment of transient middle cerebral artery occlusion in rat

The effect of anti-intercellular adhesion molecule-1 (anti-ICAM-1) antibody treatment of transient (2 h) middle cerebral artery (MCA) occlusion in the rat was measured using diffusion (DWI)-, T₂ (T2I)- and perfusion (PWI)-weighted magnetic resonance imaging. Rats were treated upon reperfusion with an anti-ICAM-1 monoclonal antibody (n=11) or a control antibody (n=7). DWI, T2I and PWI were performed before, during, and after induction of focal cerebral ischemia from 1 h to 7 days. In both groups, the apparent diffusion coefficient of water (ADC_w) and cerebral blood flow (CBF) values in the ischemic region significantly declined from the preischemic ADC_w values (p<0.05). The post ischemic increase in T₂ of the control group was significantly higher at 48 h than in the anti-ICAM-1 treated group (p<0.05). CBF was not significantly different between the two groups. The temporal profiles of MRI cluster analysis, which combines ADC_w and T₂ maps into a single image, was significantly different between groups. These data suggest that the neuroprotective effect of anti-ICAM-1 antibody treatment is reflected in reductions of T₂ and lesion growth during reperfusion and may not be associated with increased cerebral perfusion.     

Evolution of the diffusion-weighted signal and the apparent diffusion coefficient in the late phase after minor stroke

Introduction Diffusion-weighted imaging (DWI) is mainly used in acute stroke, and signal evolution in the acute phase has been studied extensively. However, patients with a minor stroke frequently present late. Recent studies suggest that DWI may be helpful at this stage, but only very few published data exist on the evolution of the DW-signal in the weeks and months after a stroke. We performed a follow-up study of DWI in the late stages after a minor stroke. Methods 28 patients who presented 48 hours to 14 days after a minor stroke underwent serial MRI at baseline, 4 weeks, 8 weeks, 12 weeks, 6 months and ≥9 months after their event. Signal intensity within the lesion was determined on T2-weighted images, DW-images and the Apparent Diffusion Coefficient (ADC) map at each time-point, and ratios were calculated with contralateral normal values (T2_r, DWI_r, ADC_r). Results T2_r was increased in all patients from the beginning, and showed no clear temporal evolution. ADC_r normalized within 8 weeks in 83% of patients, but still continued to increase for up to 6 months after the event. The DW-signal decreased over time, but was still elevated in 6 patients after ≥6 months. The evolution of ADC_r and DWI_r showed statistically highly significant inter-individual variation (p < 0.0001), which was not accounted for by age, sex, infarct size or infarct location. Conclusion The ADC and the DW-signal may continue to evolve for several months after a minor ischaemic stroke. Signal evolution is highly variable between individuals. Further studies are required to determine which factors influence the evolution of the ADC and the DW-signal. Received in revised form: 14 April 2006     

Combined application of MRS and DWI can effectively predict cell proliferation and assess the grade of glioma: A prospective study

In order to assess combined application of MRS and DWI for prediction cell proliferation and grade diagnosis of glioma, We prospectively collected the Cho/Cr, Cho/NAA, Cr/NAA of MRS and tumor parenchyma ADC (ADC_T), contralateral mirror brain tissue ADC (ADC_H), rADC (rADC = ADC_T/ADC_H). According to postoperative pathology, the patients were divided into two groups: LGG group and HGG group, compared differences of age, gender, Ki67, MRS, DWI between two groups. Next, we analyzed the correlation between MRS, DWI and Ki67. On this basis, the sensitivity and specificity of MRS, DWI and MRS combined with DWI (MRS + DWI) in diagnosis of glioma grade were evaluated. The differences of Ki67, Cho/Cr, Cho/NAA, Cr/NAA, ADC_T, rADC between LGG group and HGG group were statistically significant (p = 0.000, 0.000, 0.000, 0.008, 0.000, and 0.000 respectively). From ROC curve, area under the curve (AUC), sensitivity and specificity of Cho/Cr, Cho/NAA, Cr/NAA, ADC_T, rADC, PRE (MRS + DWI) were (0.901, 86.7%, 85.7%), (0.876, 80.0%, 82.1%), (0.704, 63.3%, 71.4%), (0.862, 82.1%, 83.3%), (0.820, 75.0%, 76.7%), (0.920, 86.7%, 89.3%), respectively. Fisher's linear discriminant functions results suggest: Y₁ = -20.447 + 3.46•X₁ + 17.141•X₂ (LGG), Y₂ = -19.415 + 4.828•X₁ + 14.543•X₂ (HGG). Our study suggested that MRS and DWI can effectively predict cell proliferation preoperative. MRS combined with DWI can further improve sensitivity and specificity in assessing the grade of glioma.     

Brain Diffusivity and Structural Changes in the R6/2 Mouse Model of Huntington Disease

Diffusion‐weighted magnetic resonance (DW‐MR) is an important diagnostic tool in Huntington disease (HD), a fatal hereditary neurodegenerative disorder. To clarify the nature of diffusivity changes in HD, we compared the apparent diffusion coefficient of water (ADC_W) acquired by DW‐MR with extracellular space volume fraction α and tortuosity λ, measured by the iontophoretic method in the R6/2 mouse model of HD and in wild‐type controls (WT). In anisotropic globus pallidus (GP), diffusion measurements were performed in the mediolateral (x ), rostrocaudal (y ), and ventrodorsal (z ) axes. In HD animals, we detected an increase in ADC_W in all axes and larger α than in WT mice. No significant difference between WT and HD mice was found in the values of tortuosity (λ_x, λ_y, λ_z). Despite structural changes in GP, diffusion anisotropy was unaffected in HD mice. Immunohistochemical analysis revealed in HD mice weaker expression of extracellular matrix and a decrease in neuron numbers compared with WT mice. Glial fibrillary acidic protein staining detected astrogliosis‐like changes in the morphology of astrocytic processes in HD GP. In the somatosensory cortex, no significant differences in the studied parameters were found. We conclude that in the R6/2 model of HD, a decrease in the number of neurons in the GP results in increased ADC_W and α values. Values of λ were not significantly changed as the increase of diffusion obstacles formed by reactive astrocytes was compensated for by the extracellular matrix reduction. © 2016 Wiley Periodicals, Inc.     

Effect of changes in optic nerve elasticity on central retinal artery blood flow in patients with idiopathic intracranial hypertension

PurposeTo assess changes in central retinal artery (CRA) blood flow by orbital color-coded Doppler ultrasonography in patients with idiopathic intracranial hypertension (IIH) and their relation with optic nerve (ON) elasticity assessed by shear wave elastography (SWE).MethodsThis study was carried out on 68 eyes of patients diagnosed with IIH and 32 eyes of healthy controls. The severity of papilledema in IIH patients was sub-classified into mild and moderate/severe groups. Color-coded Doppler was used to measure peak systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (V_mean) and pulsatility index (PI) of the CRA.ResultsPSV, V_mean, and SWE were significantly higher in patients with IIH than in controls (p = 0.001). The optimal cut-off values of PSV and V_mean for differentiating IIH patients from controls were 11.25 and 6.75 cm/s with AUC 0.81 and 0.785 respectively. AUC was 0.92 and accuracy 91% for combined PSV, V_mean and SWE differentiation between IIH patients and controls. PSV, V_mean and SWE were significantly different between mild versus moderate/severe papilledema (p = 0.001). PSV and V_mean were correlated with papilledema (r = 0.790 and 0.722 respectively) and SWE (r = 0.818 and 0.761 respectively).ConclusionIIH is associated with decreased ON elasticity and reduced CRA blood flow. Individual and combined color-coded Doppler of the CRA and SWE help in diagnosis of IIH. CRA hemodynamic changes are correlated with papilledema severity and with the extent of biomechanical changes in the ON represented by SWE.     

Cerebral blood flow characteristics in patients with post-lumbar puncture headache

The aim of this study was to verify if diagnostic lumbar puncture (DLP) in post-lumbar puncture headache (PLPH) patients is related to significant changes in cerebral blood flow which could be visualized by transcranial Doppler (TCD). Sixty-six patients were enrolled in this study. TCD was performed 24 h before DLP and repeated within 24 h after the procedure. The measurements included mean velocity (V _mean), peak systolic velocity (V _max), and Gosling’s pulsatility index (PI), in the left and right middle cerebral artery (MCA). PLPH was observed in 21 patients (32%). No significant differences were noted in V _mean, V _max and PI between the right and left MCAs—both before DLP and following this procedure. In patients who developed PLPH, bilateral pre-puncture values of V _mean and V _max were significantly higher and PI was significantly lower compared to unaffected individuals. No significant differences were observed between these groups in terms of post-puncture V _mean and V _max, but the post-puncture PI was still significantly lower in PLPH cases. In PLPH cases, the post-puncture values of V _mean and V _max were significantly lower than the respective baseline parameters. A significant inverse correlation was present between PLPH severity and bilateral pre-puncture PI. In conclusion, this study revealed that higher baseline values of V _mean and V _max and low PI in bilateral MCAs predispose patients to PLPH.     

GABA and glutamate receptors have different effects on excitability and are differentially regulated by calcium in spider mechanosensory neurons

GABA and glutamate receptors belonging to the ligand‐gated chloride‐channel family are primary targets of insecticides and antiparasitics, so their molecular structure, pharmacology and biophysical properties have attracted significant attention. However, little is known about the physiological roles of these channels or how they regulate neuronal excitability and animal behavior. Mechanosensory neurons of VS‐3 slit sensilla in the patella of the tropical wandering spider, Cupiennius salei, react to the GABA_A‐receptor agonists, GABA and muscimol, with depolarization and an increase in intracellular [Ca²⁺] and, during random noise stimulation, with a mixed inhibitory–excitatory response. We established that the GABA_A‐receptors in all VS‐3 neurons are identical, but there are at least two types of glutamate receptors and some neurons do not respond to glutamate at all. Immunohistochemistry with antibodies against Drosophila inhibitory glutamate receptor (GluCls) α‐subunit suggests that in addition to VS‐3 neurons, these receptors may also be present in the efferent neurons surrounding the sensory neurons. Most VS‐3 neurons were inhibited but not depolarized by glutamate during random stimulation, but some depolarized and had a similar excitatory–inhibitory response to glutamate as to muscimol. The membrane‐permeable Ca²⁺‐chelator BAPTA‐AM abolished muscimol effects but potentiated glutamate effects, indicating that GABA and glutamate receptors are differentially modulated by Ca²⁺, leading to diverse regulation of neuronal excitability. We hypothesize that this could be achieved by different Ca²⁺‐triggered phosphorylation processes at each receptor type. These findings are important for understanding the significance of Ca²⁺‐mediated regulation of transmitter receptor molecules and its role in controlling excitability.     

Balanced modulation of striatal activation from D2/D3 receptors in caudate and ventral striatum: Disruption in cannabis abusers

Proper communication between dorsal caudate (CD) and ventral striatum (VS) is likely to be crucial for on‐time responses and its disruption might result in impulsivity. Here, we used functional magnetic resonance imaging (fMRI) with a sensorimotor reaction time task and positron emission tomography (PET) with [¹¹C]raclopride in 14 healthy controls and 18 cannabis abusers to contrast the modulation of striatal fMRI responses by dopamine receptors (D₂/D₃R) in CD and VS. In controls, we show that the fMRI signals in VS that occurs concomitantly with on‐time responses showed opposite modulation from D₂/D₃R in CD (inhibitory) and D₂/D₃R in VS (stimulatory). In contrast, this modulation was not significant in cannabis abusers. Findings suggest that action speed requires balanced VS‐inhibition from D₂/D₃R in CD and VS‐facilitation from D₂/D₃R in VS. Hum Brain Mapp 36:3154–3166, 2015. © 2015 Wiley Periodicals, Inc.     

Cerebrovascular and cardiovascular responses associated with orthostatic intolerance and tachycardia

Idiopathic orthostatic intolerance syndrome is characterized by postural symptoms of cerebral hypoperfusion without arterial hypotension. Abnormal baroreceptor responses with deranged cerebral autoregulation leading to cerebral vasoconstriction have been proposed as a causative mechanism. The authors report the cerebrovascular and cardiovascular responses in a patient who recovered from orthostatic intolerance and tachycardia. Changes in the orthostatic responses of mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and transcranial Doppler middle cerebral artery (MCA) mean blood flow velocity (V_mean) were assessed at admission and again 6 months after recovery. Normal cardiovascular responses to forced breathing and to standing indicated intact overall baroreflex integrity with normal baroreflex sensitivity (10.2 msec·mm Hg⁻¹). After the patient stood for 8 minutes, presyncopal symptoms developed, with unchanged MAP but increased HR (+41 beats/min) and reduced stroke volume (SV) (−69%), CO (−50%), and MCA V_mean (−46%; 57 to 31 cm·s⁻¹). After a reconditioning program and recovery, the patient was reexamined. The supine MCA V_mean was larger (79 cm·s⁻¹), as were MAP (76 versus 70 mm Hg) and CO (+15%). The orthostatic HR increase was smaller (+5 beats/min), as was the reduction in SV (−44%) and CO (−30%), with an increase in MAP to 93 mm Hg. The orthostatic reduction in MCA V_mean was smaller (−13 versus −26 cm·s⁻¹) and standing cerebrovascular resistance decreased (1.41 versus 2.39 mm Hg·cm·s⁻¹). In this patient who had intact baroreflex control and no postural decrease in blood pressure, the reduction in MCA V_mean, concomitant with a large decrease in CO, seemed reversible. The result suggests that a symptomatic reduction in cerebrovascular conductance during standing is to be interpreted as being an adaptive response to a critically limited systemic blood flow, rather than to derangement of cerebral autoregulation.     

A deficiency of the link protein Bral2 affects the size of the extracellular space in the thalamus of aged mice

Bral2 is a link protein stabilizing the binding between lecticans and hyaluronan in perineuronal nets and axonal coats (ACs) in specific brain regions. Using the real‐time iontophoretic method and diffusion‐weighted magnetic resonance, we determined the extracellular space (ECS) volume fraction (α), tortuosity (λ), and apparent diffusion coefficient of water (ADC_W) in the thalamic ventral posteromedial nucleus (VPM) and sensorimotor cortex of young adult (3–6 months) and aged (14–20 months) Bral2‐deficient (Bral2^?/?) mice and age‐matched wild‐type (wt) controls. The results were correlated with an analysis of extracellular matrix composition. In the cortex, no changes between wt and Bral2^?/? were detected, either in the young or aged mice. In the VPM of aged but not in young Bral2^?/? mice, we observed a significant decrease in α and ADC_W in comparison with age‐matched controls. Bral2 deficiency led to a reduction of both aggrecan‐ and brevican‐associated perineuronal nets and a complete disruption of brevican‐based ACs in young as well as aged VPM. Our data suggest that aging is a critical point that reveals the effect of Bral2 deficiency on VPM diffusion. This effect is probably mediated through the enhanced age‐related damage of neurons lacking protective ACs, or the exhausting of compensatory mechanisms maintaining unchanged diffusion parameters in young Bral2^?/? animals. A decreased ECS volume in aged Bral2^?/? mice may influence the diffusion of neuroactive substances, and thus extrasynaptic and also indirectly synaptic transmission in this important nucleus of the somatosensory pathway.     

ADC直方图鉴别脑转移瘤病理性质的价值

目的 探讨ADC直方图在腺癌脑转移瘤和鳞癌脑转移瘤鉴别诊断中的价值。方法 回顾性分析经病理证实的48例脑转移瘤（腺癌31例,鳞癌17例）术前磁共振弥散加权成像,绘制整个肿瘤的ADC直方图,并计算出最小ADC值（ADCmin）、最大ADC值（ADCmax）、平均ADC值（ADCmean）、第5百分位数（ADC_5th）、第25百分位数（ADC_25th）、中位数（ADC_50th）、第75百分位数（ADC_75th）、第95百分位数（ADC_95th）。结果 腺癌脑转移瘤ADCmin、ADCmean、ADCmax均明显高于鳞癌脑转移瘤（P<0.05）,但是两种性质脑转移瘤ADC_5th、ADC_25th、ADC_50th、ADC_75th、ADC_95th均未见显著性差异（P>0.05）。根据ROC曲线分析结果,以ADCmin=0.600×10-3 mm2/s为阈值鉴别腺癌脑转移瘤和鳞癌脑转移瘤时,诊断效能最佳,ROC曲线下面积最大,为0.700,诊断灵敏度为64.7%,特异度为74.2%。结论 ADC直方图可以提供肿瘤的整体信息,有助于鉴别诊断腺癌脑转移瘤与鳞癌脑转移瘤。     

Exploring the relationship between social attachment and dopamine D2/3 receptor availability in the brains of healthy humans using [11C]-(+)-PHNO

Differences in striatal dopamine (DA) function may be related to differences in the degree of social attachment to others. Using positron emission tomography (PET), socially detached persons demonstrate reduced DA D_2/3 receptor (D_2/3R) availability in the striatum. However, previous PET studies have only used antagonist radiotracers for D_2/3R and have not specifically examined regions of interest (ROIs) such as the ventral striatum (VS). In 32 healthy persons, we investigated the relationship between self-reported attachment and DA D_2/3R availability in striatal and extrastriatal ROIs as measured using the agonist radiotracer [¹¹C]-(+)-PHNO. Surprisingly, more social attachment—as measured by the attachment subscale of the temperament and character inventory—was related to less [¹¹C]-(+)-PHNO binding in the VS (r(30) = ?.43, p = .01). This relationship held in a subsample who also completed the detachment subscale of the Karolinska Scales of Personality (r(10) = .62, p = .03). However, no relationships were observed with BP_ND in the dorsal striatum or D₃R-specific ROIs. One potential explanation for these findings is that persons who are more socially detached have less endogenous DA occupying D_2/3R in the VS. This interpretation warrants investigation by future research. These findings may help us better understand the neurochemical basis of attachment.     

Apparent diffusion coefficient of the superior cerebellar peduncle differentiates progressive supranuclear palsy from Parkinson's disease

The early diagnosis of progressive supranuclear palsy (PSP) may be challenging, because of clinical overlapping features with Parkinson's disease (PD) and other parkinsonian syndromes such as the Parkinsonian variant of multiple system atrophy (MSA‐P). Conventional MRI can help in differentiating parkinsonian disorders but its diagnostic accuracy is still unsatisfactory. On the basis of the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in patients with PSP, we assessed the SCP apparent diffusion coefficient (ADC) values in patients with PSP, PD, and MSA‐P in order to evaluate its differential diagnostic value in vivo. Twenty‐eight patients with PSP (14 with possible‐PSP and 14 with probable‐PSP), 15 PD, 15 MSA‐P, and 16 healthy subjects were studied by using diffusion weighted imaging (DWI). ADC was calculated in regions of interest defined in the left and right SCP by two clinically blinded operators. Intrarater (r = 0.98, P < 0.001) and interrater reliability (r = 0.97; P < 0.001) for SCP measurements were high. Patients with PSP had higher SCP rADC values (median 0.98 × 10^?3mm²/s) than patients with PD (median 0.79 × 10^?3 mm²/s, P < 0.001), MSA‐P (median 0.79 × 10^?3 mm²/s, P < 0.001), and healthy controls (median 0.80 × 10^?3 mm²/s, P < 0.001). DWI discriminated patients with PSP from PD and healthy subjects on the basis of SCP rADC individual values (100% sensitivity and specificity) and from patients with MSA‐P (96.4% sensitivity and 93.3% specificity). The higher values of rADC in SCP of patients with PSP correspond with the in vivo microstructural feature of atrophy detected postmortem and provide an additional support for early discrimination between PSP and other neurodegenerative parkinsonisms. © 2008 Movement Disorder Society     

Preliminary characterization of synaptic vesicle/calmodulin interaction

The association of calmodulin with brain synaptic vesicle proteins was analyzed. Scatchard analysis of [¹²⁵I]calmodulin binding to brain synaptic vesicles revealed one high-affinity, low-binding-capacity,K_d = 1.0 (± 0.15)nM,B_max = 4.1 (± 0.6)pmol/mg, and one low-affinity high-binding-capacity site,K_d = 177. (± 12.0)nM andB_{max= 202 (± 15.0)pmol/mg}. Triton X-100 solubilization of synaptic vesicle proteins and subsequent elution on a Sepharose-4B-CNBr-calmodulin affinity column demonstrated that two protein doublets of approximate M_r^S 55 K and 30 K were the major synaptic vesicle calmodulin binding proteins. In addition there were two minor calmodulin binding singlet polypeptides with M_r^S 62 K and 40 K. Calmodulin stimulated endogenous synaptic vesicle protein kinase, Ca²⁺,Mg⁺-ATPase and Ca²⁺ uptake activities. Phosphorylation assays coupled with immunological studies using affinity-purified antibodies suggested that the synaptic vesicle Ca²⁺/calmodulin-dependent protein kinase migrated in the 30 K M_r region.     

Effects of mammalian brain extracts and chlormadinone acetate on neuronal Na, K-ATPase and electrogenic Na, K-pump activity in vitro

Acid-acetone extracts of brain (from beef and guinea pig) and chlormadinone acetate (CMA) were compared with ouabain for their ability to inhibit the electrogenic Na⁺,K⁺-pump and the Na⁺,K⁺-ATPase of neuronal tissues. The membrane potential of neurones in the paravertebral sympathetic ganglion of the bullfrog was recorded in K⁺-free Ringer's solution by means of the sucrose gap technique. The potassium activated hyperpolarization (K_H⁺), induced by the re-introduction of potassium, was used as an index of electrogenic Na⁺,K⁺-pumping. The K_H⁺ was blocked by 1 μM ouabain. Na⁺,K⁺-ATPase activity was measured in microsomal membrane preparations of frog and beef brain using a continuous spectrophotometric assay. Although ouabain consistently inhibited beef brain Na⁺,K⁺-ATPase (IC₅₀ = 2.2 μM), acid-acetone extracts prepared from guinea pig and beef brain produced only partial inhibition. Neither of the extracts significantly reduced the K_H⁺ of the frog ganglion. CMA inhibited Na⁺,K⁺-ATPase prepared from bullfrog brain and spinal cord with slightly greater potency (IC₅₀ = 4.5 μM) than did ouabain (IC₅₀ = 10 μM). In contrast, electrogenic Na⁺,K⁺-pumping (i.e. the K_H⁺) in the frog ganglion was not affected by this steroid. It is concluded that although both the extracts and CMA inhibited Na⁺,K⁺-ATPase, neither can be considered ouabain-like due to their failure to affect the electrogenic Na⁺,K⁺-pump in situ.     

White matter diffusion is higher in Binswanger disease than in idiopathic normal pressure hydrocephalus

Objectives – To explore diagnostic differences in periventricular white matter (PWM) and deep white matter (DWM) diffusion patterns in patients diagnosed with Binswanger disease (BD) and in patients diagnosed with probable idiopathic normal pressure hydrocephalus (INPH) using diffusion‐weighted imaging (DWI). Materials and methods – Apparent diffusion coefficient (ADC) values were calculated in the PWM and DWM in patients with INPH (n = 14) and BD (n = 9) and in controls (n = 10) using an spin echo echo planar imaging single‐shot diffusion sequence and region of interest (ROI) analysis. Results – Patients with BD had higher ADC values than patients with INPH in the PWM and DWM in the frontal and occipital regions (P < 0.05) and higher values than controls in the frontal PWM and DWM (P < 0.01). After shunt surgery, ADC values were reduced in the frontal PWM in patients with INPH (P < 0.05). Conclusions – Increased diffusion in the PWM and DWM in patients with BD may reflect irreversible breakdown of axonal integrity caused by the subcortical ischaemic vascular disease. By contrast, the normal white matter diffusion in patients with INPH indicates structurally intact axons, compatible with the reversibility of this disorder. DWI may be an important non‐invasive diagnostic tool for differentiating between INPH and BD and identifying shunt responders and reversible brain damage in patients with INPH. However, the overlap between patients with INPH and BD in this study restricts the predictive value of the method.