Literatura académica sobre el tema "Volume lesionale"

Background Cerebrospinal fluid circulation is crucial for the functioning of the brain. Aging and brain pathologies such as Alzheimer’s disease have been associated with a change in the morphology of the ventricles and the choroid plexus. Despite the evidence from animal models that the cerebrospinal fluid system plays an important role in neuroinflammation and the restoration of the brain after ischemic brain injury, little is known about changes to the choroid plexus after stroke in humans. Aims Our goal was to characterize structural choroid plexus changes poststroke. Methods We used an automatic segmentation tool to estimate the volumes of choroid plexus and lateral ventricles in stroke and control participants at three time points (at baseline, 3 and 12 months) over the first year after stroke. We assessed group differences cross-sectionally at each time point and longitudinally. For stroke participants, we specifically differentiated between ipsi- and contra-lesional volumes. Statistical analyses were conducted for each region separately and included covariates such as age, sex, total intracranial volume, and years of education. Results We observed significantly larger choroid plexus volumes in stroke participants compared to controls in both cross-sectional and longitudinal analyses. Choroid plexus volumes did not exhibit any change over the first year after stroke, with no difference between ipsi- and contra-lesional volumes. This was in contrast to the volume of lateral ventricles that we found to enlarge over time in all participants, with more accelerated expansion in stroke survivors ipsi-lesionally. Conclusions Our results suggest that chronic stages of stroke are characterized by larger choroid plexus volumes, but the enlargement likely takes place prior to or very early after the stroke incident.

Background: The short-term effect of corticosteroids on MRI measures of multiple sclerosis (MS) is not well understood and may have a significant impact when using these quantitative measures to evaluate disease activity and changes following other therapeutic interventions. Objective: To determine the impact of a course of intravenous methylprednisolone (IVMP) on quantitative measures of disease activity and tissue injury in MS patients. Methods: We prospectively measured brain parenchymal fraction (BPF), magnetization transfer ratio (MTR, lesional and whole brain), and lesion volumes on nine weekly brain MRI studies in ten MS patients receiving a course of IVMP. A group of nine MS patients not receiving IVMP served as controls. Results: In comparison to untreated controls, BPF declined over the eight weeks following IVMP treatment (P<0.02). BPF decline was most prominent in patients with secondary progressive MS (SPMS, P<0.03), and was not seen in relapsing-remitting (RR) MS patients. Short-term change in BPF correlated with baseline BPF (r=0.62, P=0.05) and short-term change in lesional MTR (r=-0.55, P=0.03), but not with change in enhancing lesion volume. Short-term change in lesional MTR inversely correlated with baseline lesional and whole brain MTR (r=-0.79, P=0.04 for both). There was no significant difference between treated and control patients in measures of MTR or T2, T1 or enhancing lesion volumes. Conclusions: Patients with SPMS showed a greater decline in BPF following IVMP than RRMS patients. A correlation between changes in BPF and MTR suggest that these changes are secondary to altered water content within MS lesions. Differential response to a standardized therapeutic intervention in RRMS and SPMS suggests that responses to therapy may differ due to a fundamental pathologic difference between early and late stage MS.

Abstract BACKGROUND Meningiomas are common intracranial tumors which usually carry a benign prognosis. Some meningiomas cause perifocal edema which might indicate that this subset could interfere with normal brain function. Resting-state functional MRI (rsfMRI) can be used to assess whole brain functional connectivity (fc) which can be used as a marker for disease severity in patients with intracranial tumors, as was recently shown by our group in a cohort of glioma patients. In this study, we investigated whether the presence of perifocal edema in preoperative patients with meningioma leads to fc. METHODS Patients with suspected meningioma were prospectively included and functional resting state MRI scans were obtained. The resulting data was processed according to our recently published method and abnormality of fc was quantified for each individual patient. Abnormality of fc was then correlated with tumor and edema volume as well as WHO grade. RESULTS 26 patients (23 WHO grade I, 3 WHO grade II) were included. 13 patients had perifocal edema. There was a highly significant correlation between edema volume and higher abnormality of fc both in the lesional and the contra-lesional hemisphere (r=0.51, p=0.008 and r=0.61, p=0.001). Patients with no perifocal edema showed only very low abnormality of fc. Tumor volume was not correlated with abnormal fc in both the lesional and the contralesional hemispheres (r=0.23, p=0.27 and r=0.28, p=0.17). There was also no significant correlation between WHO grade and abnormality of fc. CONCLUSION RsfMRI showed significant abnormal fc in meningioma patients with perifocal edema in contrast to patients without edema, independent of tumor volume. This demonstrates that the presence of edema but not the tumor volume is relevant for disturbances of fc.

OBJECTIVEConcurrent use of anti-PD-1 therapies with stereotactic radiosurgery (SRS) have been shown to be beneficial for survival and local lesional control in melanoma patients with brain metastases. It is not known, however, if immunotherapy (IT) confers the same outcome advantage in lung cancer patients with brain metastases treated with SRS.METHODSThe authors retrospectively reviewed 85 non–small cell lung cancer (NSCLC) patients with brain metastases who were treated with SRS between January 2006 and December 2016. Thirty-nine PD-L1 antibody–positive patients received anti-PD-1 therapy with SRS (IT group) and 46 patients received chemotherapy (CT) with SRS (CT group). Results were obtained using chi-square, Kaplan-Meier, and Mann-Whitney U tests and Cox regression analyses.RESULTSMedian survival following first radiosurgical treatment in the whole study group was 11.6 months (95% CI 8–15.5 months). Median survival times in the IT group and CT group were 10 months (95% CI 8.3–13.2 months) and 11.6 months (95% CI 7.7–15.6 months), respectively (p = 0.23). A Karnofsky Performance Status (KPS) score < 80 (p = 0.001) and lung-specific molecular marker Graded Prognostic Assessment (lungmol GPA) score < 1.5 (p = 0.02) were found to be predictive of worse survival.Maximal percent lesional shrinkage and time to maximal shrinkage were not significantly different between the CT and IT groups. Of the lesions for which a complete response occurred, 94.8% had pre-SRS volumes < 500 mm3. The amount of lesion shrinkage and time to maximal shrinkage were not different between the IT and CT groups for lesions with volumes < 500 mm3. However, in lesions with volume > 500 mm3, 90% of lesions shrank after radiosurgery in the IT group compared with 47.8% in the CT group (p = 0.001). Median times to initial response and times to maximal shrinkage were faster in the IT group than in the CT group: initial response 49 days (95% CI 33.7–64.3 days) versus 84 days (95% CI 28.1–140 days), p = 0.001; maximal response 105 days (95% CI 59–150 days) versus 182 days (95% CI 119.6–244 days), p = 0.12.CONCLUSIONSUnlike patients with melanoma, patients with NSCLC with brain metastases undergoing SRS showed no significant benefit—either in terms of survival or total amount of lesional response—when anti-PD-1 therapies were used. However, in lesions with volume > 500 mm3, combining SRS with IT may result in a faster and better volumetric response which may be particularly beneficial in lesions causing mass effect or located in neurologically critical locations.

Clinical studies have revealed a strong link between increased burden of cerebral microinfarcts and risk for cognitive impairment. Since the sum of tissue damage incurred by microinfarcts is a miniscule percentage of total brain volume, we hypothesized that microinfarcts disrupt brain function beyond the injury site visible to histological or radiological examination. We tested this idea using a mouse model of microinfarcts, where single penetrating vessels that supply mouse cortex were occluded by targeted photothrombosis. We found that in vivo structural and diffusion MRI reliably reported the acute microinfarct core, based on spatial co-registrations with post-mortem stains of neuronal viability. Consistent with our hypothesis, c-Fos assays for neuronal activity and in vivo imaging of single vessel hemodynamics both reported functional deficits in viable peri-lesional tissues beyond the microinfarct core. We estimated that the volume of tissue with functional deficit in cortex was at least 12-fold greater than the volume of the microinfarct core. Impaired hemodynamic responses in peri-lesional tissues persisted at least 14 days, and were attributed to lasting deficits in neuronal circuitry or neurovascular coupling. These data show how individually miniscule microinfarcts could contribute to broader brain dysfunction during vascular cognitive impairment and dementia.

Intracerebral hemorrhage (ICH) is the most severe form of stroke. Catheter-delivered thrombolysis with recombinant tissue-type plasminogen activator (rtPA) for the drainage of ICH is currently under evaluation in a phase III clinical trial (MISTIE III). However, in a pig model of ICH, in situ fibrinolysis with rtPA was reported to increase peri-lesional edema by promoting N-methyl-D-aspartate (NMDA)-dependent excitotoxicity. In the present study, we engineered a non-neurotoxic tPA variant, OptPA, and investigated its safety and efficacy for in situ fibrinolysis in a rat model of ICH. Magnetic resonance imaging analyses of hematoma and edema volumes, behavioral tasks and histological analyses were performed to measure the effects of treatments. In vitro, OptPA was equally fibrinolytic as rtPA without promoting NMDA-dependent neurotoxicity. In vivo, in situ fibrinolysis using OptPA reduced hematoma volume, like rtPA, but it also reduced the evolution of peri-hematomal neuronal death and subsequent edema progression. Overall, this preclinical study demonstrates beneficial effects of OptPA compared to rtPA for the drainage of ICH.

Background and Purpose— We examined if ischemic stroke is associated with white matter degeneration predominantly confined to the ipsi-lesional tracts or with widespread bilateral axonal loss independent of lesion laterality. Methods— We applied a novel fixel-based analysis, sensitive to fiber tract–specific differences within a voxel, to assess axonal loss in stroke (N=104, 32 women) compared to control participants (N=40, 15 women) across the whole brain. We studied microstructural differences in fiber density and macrostructural (morphological) changes in fiber cross-section. Results— In participants with stroke, we observed significantly lower fiber density and cross-section in areas adjacent, or connected, to the lesions (eg, ipsi-lesional corticospinal tract). In addition, the changes extended beyond directly connected tracts, independent of the lesion laterality (eg, corpus callosum, bilateral inferior fronto-occipital fasciculus, right superior longitudinal fasciculus). Conclusions— We conclude that ischemic stroke is associated with extensive neurodegeneration that significantly affects white matter integrity across the whole brain. These findings expand our understanding of the mechanisms of brain volume loss and delayed cognitive decline in stroke.

166 Background: 177Lutetium PSMA-617 (LuPSMA) is an effective therapy for metastatic castrate-resistant prostate cancer (mCRPC). However, treatment resistance may occur. We developed a quantitative workflow for serial PSMA PET/CT to optimise predictive and prognostic imaging biomarker capability for progression free (PFS) and overall survival (OS). Methods: 56 men with mCRPC previously treated with taxane chemotherapy and androgen signaling inhibitor were enrolled, receiving up to 6 doses of LuPSMA and a radiation sensitizer idronoxil (NOX66). 68Ga-PSMA-11 PET/CT was performed at study entry and exit. Traffic Light (TL) quantification workflow was developed to track changes in both tumour volume and intensity at a total body and lesional level. Lesions were classified as responding in green (>30% decline in volume), stable in yellow (<30% change in volume/intensity), progressive in red (>30% increase in volume/intensity, or new). Overall response pattern was categorised as responding ( green/yellow), low volume red (<50% progressive disease) or high volume red (>50% progressive disease). TL workflow results were correlated with PFS and OS. Results: 37/56 men underwent both entry and exit imaging. The median PSA decline was 77% (IQR 34-92%), and 70% (26/37) achieved PSA response >50%. PSA progression occurred in 54% (20/37) at exit imaging. Median PFS was 8.6 months (95%CI 5.6-11.6) and median OS 22 months (95% CI 18.6-25.6). 95% (35/37) had reduction in PSMA SUVmax (-26.1 (IQR +11.7 to -89.4)) and SUVmean (-3.3 (+2.9 to -14.2)). PSMA total tumor volume reduced in 68% (25/37) (median -0.64 liters (range +1.44 to -1.1)). On TL workflow, 24% (9/37) had responding/stable disease ( green/ yellow), 76% (28/37) had progressive disease ( red) of whom 41% (15/37) had low volume progression and 35% (13/37) high volume progression. Men with high volume progression had worse OS compared to responders (HR 0.18 (0.05-0.59), p 0.005), and low volume progression (HR 0.30 (0.11-0.80), p 0.02). 68% (19/28) had progression on both TL workflow and PSA, while 32% (9/28) had progression on TL workflow without PSA progression. In multivariable analysis, TL workflow and PSA progression at time of exit scans were independent predictors of OS (Table). Conclusions: This study demonstrates the feasibility of characterizing lesional response on molecular imaging with a quantification TL workflow. TL workflow response independently correlated with survival outcomes, indicating serial PSMA PET has prognostic biomarker potential. Clinical trial information: ACTRN12618001073291.[Table: see text]

Trabalho de Projeto do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
Introdução: CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy) é atualmente a causa hereditária mais comum de acidente vascular cerebral (AVC) e demência vascular nos adultos. Este estudo tem como objetivo comparar as características clínicas, hemodinâmicas e imagiológicas dos doentes com CADASIL com voluntários saudáveis e investigar, naqueles com a doença, se há associação entre a presença de refluxo jugular venoso (RJV) e o volume lesional cerebral.Métodos: Foram incluídos doentes com CADASIL acompanhados na consulta de Risco Vascular do Serviço de Neurologia do Centro Hospitalar e Universitário de Coimbra (CHUC). A população controlo foi composta por voluntários saudáveis. Foram recolhidos dados sobre os fatores de risco vascular. Os doentes e os controlos foram submetidos ao estudo vascular extra e intracraniano recorrendo a ultrassonografia-Doppler, que incluiu análise do fluxo sanguíneo cerebral (CBF), fluxo sanguíneo venoso (VBF) e fluxo da veia jugular interna (IJV) durante as manobras de Valsalva. Os participantes também foram submetidos a estudo de imagem cerebral, com recurso a ressonância magnética (3-Tesla) tendo sido utilizado um algoritmo de cálculo de crescimento de lesão para determinar o volume lesional cerebral. O teste χ2 foi usado para variáveis nominais (ou o teste exato de Fisher, quando apropriado) e o t-test para variáveis contínuas. Quando o ajuste para variáveis confundentes foi necessário, a regressão logística binária (variáveis nominais) e a regressão linear (variáveis contínuas) foram utilizadas. Significância estatística foi considerada em todos os resultados com um p<0.05.Resultados: Foram incluídos 55 participantes (28 doentes com CADASIL e 27 controlos). Neste estudo, 30.9% apresentaram RJV (todos detetados durante manobras de Valsalva). A presença de RJV foi semelhante nos doentes com CADASIL quando comparados com o grupo controlo (OR 1.04; CI 95%: 0.22 – 5.00; p=0.958). Também não foi observada uma diferença estatisticamente significativa no fluxo sanguíneo cerebral ou fluxo sanguíneo venoso entre os dois grupos. Na população doente, a presença de RJV pareceu estar associada a maior volume lesional (β 11.86; CI 95%: -6.74 – 30.46; p=0.201) e menor número de lesões (β -4.22; CI 95%: -13.36 – 4.92; p=0.350), embora não estatisticamente significativo. No subgrupo com idade igual ou superior a 40 anos a associação foi estatisticamente significativa (β 22.14; CI 95%: 6.47 – 37.82; p=0.008).Conclusões: A nossa população de doentes com CADASIL apresentou as mesmas características clínicas típicas anteriormente descritas. A prevalência de RJV parece ser idêntica em doentes com CADASIL em comparação com controlos saudáveis. No entanto, parece existir uma tendência para o aumento de volume lesional em doentes com CADASIL e com RJV, particularmente naqueles com 40 anos ou mais. RJV pode ser um fator de risco não documentado para a progressão da doença.
Background and Purpose: CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy) is currently the most common hereditary cause of stroke and vascular dementia in adults. This study aims to compare the clinical, cerebral hemodynamic and imagiologic characteristics of CADASIL patients with healthy volunteers and to investigate, in those with the disease, if there is an association between the presence of jugular venous reflux (JVR) and brain lesion´s volume.Methods: We included willing patients with CADASIL followed in the outpatient clinic at the Neurology Department of Centro Hospitalar e Universitário de Coimbra (CHUC). The control population was composed by healthy volunteers. We collected data on vascular risk factors. Patients and controls underwent extra- and transcranial Doppler-ultrasonography (D-US) study, including analysis of cerebral blood flow (CBF), venous blood flow (VBF) and internal jugular vein (IJV) flow during Valsalva manoeuvres (VM). Magnetic Resonance Imaging (MRI) (3-Tesla) was also applied and a lesion growth algorithm calculation was used to determine brain lesion volume. χ2 test was used for nominal variables (or Fisher's exact test when appropriate) and t-test for continuous variables. When adjustment for confounding variables was needed, binary logistic regression (nominal variables) and linear regression (continuous variables) were used. Statistical significance was set at two-sided p values <0.05. Results: A total of 55 subjects (28 CADASIL patients and 27 controls) were enrolled. In this study, 30.9% had JVR (all detected during VM). CADASIL was not associated with a higher prevalence of JVR compared with the control group (OR 1.04; CI 95%: 0.22 – 5.00; p=0.958) nor there was a statistically difference in CBF or VBF between this two groups. In patients, the presence of JVR appeared to be associated with higher lesion volume (β 11.86; CI 95%: -6.74 – 30.46; p=0.201) and a lower number of lesions (β -4.22; CI 95%: -13.36 – 4.92; p=0.350), although not statistically significant. This association was significantly increased in the subpopulation of patients aged 40 years or older (β 22.14; CI 95%: 6.47 – 37.82; p=0.008).Conclusion: Our population of Portuguese CADASIL patients had the same typical clinical characteristics of others described before. The prevalence of JVR seems to be identical in CADASIL patients compared to healthy controls. However, it appears to be a trend for higher lesion volume in CADASIL patients with JVR, particularly in those aged 40 or more. JVR might be a non-documented risk factor for disease progression.

A esclerose múltipla é uma doença neurodegenerativa resultante da desmielinização do sistema nervoso central. A imagem de ressonância magnética cerebral constitui o método mais utilizado no acompanhamento e avaliação da carga lesional e atrofia cerebral, aspetos que se relacionam com o prognóstico da doença. Na prática clínica estes indicadores são avaliados visualmente, mas estudos recentes têm revelado o potencial de métodos quantitativos automáticos na complementaridade e padronização desta análise. A presente dissertação expõe o desenvolvimento de um método dessa natureza, a ser integrado no serviço de neurorradiologia do Hospital Egas Moniz (HEM). Optou-se pela criação de um plugin no programa Osirix, cujas ferramentas de análise são executadas por meio de uma pipeline construída através da linguagem de comandos bash, recorrendo a um pacote de ferramentas do MATLAB. Desenvolvida a ferramenta, de nome QuantEmTool, foram analisados um total de 19 doentes e um sujeito controlo com exames realizados no HEM, tendo sido estudada a viabilidade de utilização das sequências FLAIR e de ponderação em T1, com e sem recurso a contraste. Foi realizada uma análise estatística de forma a estudar a possível existência de correlação dos indicadores estimados com alguns dados clínicos e hábitos de risco. Verificou-se um bom desempenho na determinação dos índices de atrofia e carga lesional para todos os protocolos de imagem. Os resultados sugerem que o protocolo que recorre às sequências FLAIR e de ponderação em T1, ambas adquiridas após a injeção de contraste, apresenta bons resultados de quantificação ao mesmo tempo que permite diminuir a duração total do exame. Uma análise baseada numa amostra maior e mais heterogénea de doentes será necessária para validar os resultados obtidos. Relativamente à segunda análise, registaram-se resultados que indiciam uma correlação entre os indicadores de atrofia e de carga lesional e alguns dos dados clínicos, entre os quais se destacam a idade, a duração da doença e o grau de severidade da mesma.

Outcome funzionali a breve e lungo termine dopo riparazione immediata di frattura peniena: esperienza di un centro di riferimento ad alto volume ABSTRACT Obiettivo Valutare gli outcome post-chirurgici e funzionali nei pazienti sottoposti a riparazione di frattura peniena previa localizzazione ecografica della lesione ed esplorativa chirurgica. Materiali e Metodi Lo studio retrospettico di coorte monocentrico ha previsto il riesame delle cartelle cliniche da settembre 2004 a dicembre 2016. I criteri d’inclusione erano la documentata presenza di una lesione della tunica albuginea all’ecografia preoperatoria e alla successiva esplorativa chirurgica. Sono stati inclusi nello studio 152 pazienti su 190. Abbiamo valutato la causa d’insorgenza, la modalità di presentazione, l’aspetto ecografico, le caratteristiche intraoperatorie, i risultati funzionali e le complicanze della riparazione chirurgica. L’esatta localizzazione della lesione dell’albuginea veniva identificata ecograficamente e marcata a livello cutaneo pre-operatoriamente in modo tale da effettuare un accesso mini-invasivo e ridurre i rischi associati all’accesso subcoronale e alla circoncisione. Nel follow up a 12 mesi dall’evento traumatico abbiamo valutato la funzione sessuale e urinaria mediante somministrazione di questionari validati ed eventuale uroflussimetria per coloro i quali presentavano lesioni uretrali. E’ stata inoltre valutata l’accuratezza dell’esame ecografico nel rilevare l’esatta localizzazione del difetto del tunica albuginea. Risultati L'età media è risultata di 39,5 anni (range 21-72) e il follow-up medio di 13 settimane. L'eziologia della frattura è stato il rapporto sessuale in 140 pazienti, la manovra del “taghaandan” in 6 e il girarsi nel letto durante il sonno a pene eretto nei restanti 6. I reperti intraoperatori mostravano una lacerazione dell’albuginea ventrale e trasversale nel 90% dei casi. Le lesioni uretrali erano evidenti in un quarto dei nostri pazienti. Un deterioramento della qualità delle erezioni è stato riportato soltanto dal 5% di pazienti. Il 5,2% invece ha riportato l’insorgenza di una curvatura peniena ≤ 15° dopo l'intervento. Conclusioni La frattura peniena è un’emergenza urologica che richiede un’esplorativa chirurgica immediata con riparazione della lesione per evitare complicanze permanenti. L'ecografia rappresenta un esame a basso costo e facilmente reperibile in tutti i Pronto Soccorso che consente di confermare la diagnosi, identificando la corretta localizzazione della lacerazione dell’albuginea e delle eventuali lesioni uretrali associate.