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1.
Seizure ; 85: 145-150, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33465639

RESUMEN

PURPOSE: There are multidien patterns of seizure occurrence. Predicting seizure risk may be easier with biomarker correlates to multidien patterns. We hypothesize multiday hyper or hypoglycemia contributes to seizure risk. METHODS: In a type I diabetic (T1D) with focal onset epilepsy with continuous glucose monitoring (CGM) and responsive neurostimulation (RNS) devices, we studied multiday interictal activities (IEA), seizures, and glucose. Hourly CGM data was matched to hourly RNS captures of interictal and ictal activities over 33 months. RNS detection settings were unchanged. Multidien cycles were analyzed, active blocks of IEA and ictal episodes defined, and tissue glucose averages studied. RESULTS: Average glucose was 161 mg/dl. A 40-day cycle of interictal and ictal activities occurred, though no similar glucose cycle was evident. Glucose elevations relative to patient average were associated with increases in IEA but not seizure. Frequent seizures were not associated with obvious elevations or decreases of glucose from baseline, most seizures occurred at +/- 10 mg/dl of average daily glucose (i.e. 150-170 mg/dl). CONCLUSION: Tissue glucose may influence IEA but may not influence multiday seizure activity or very frequent seizures. In an ambulatory T1D patient multiday hypo or hyperglycemic extremes do not appear to provoke seizure activities.


Asunto(s)
Automonitorización de la Glucosa Sanguínea , Glucemia , Electroencefalografía , Glucosa , Humanos , Convulsiones
2.
Epilepsy Behav Rep ; 15: 100419, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33426516

RESUMEN

Antiseizure medications (ASM) may contribute to adverse fetal outcomes in pregnant women with epilepsy (WWE). Folate processing (Methylenetetrahydrofolate reductase, MTHFR) gene abnormalities are common in women with epilepsy and depression. L-methylfolate supplements may bypass MTHFR deficiencies, yet their use in WWE during gestation or on fetal development is not well studied. We examine pregnancy histories of three WWE who supplemented with either folate or L-methylfolate and methylcobalamin (methylated B12) during pregnancies. Their pregnancy outcomes improved with L-methylfolate and methylcobalamin supplementation. L-methylfolate and methylcobalamin supplementation merits further study in WWE who have MTHFR mutations, fertility, recurrent miscarriage and or depression histories.

3.
Br J Haematol ; 192(3): 504-513, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32621535

RESUMEN

The UK National Cancer Research Institute initiated a prospective study (UKCRN-ID 1760) to assess the prognostic value of early fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in diffuse large B-cell lymphoma (DLBCL). In total, 189 patients with DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) had baseline and post-cycle-2 PET (PET2) within a quality assurance framework. Treatment decisions were based on CT; PET2 was archived for central blinded reporting after treatment completion. The association of PET2 response with end-of-treatment CT, progression-free (PFS) and overall survival (OS) was explored. The end-of-treatment complete response rate on CT was 83·9%, 75·0%, 70·5%, 40·4% and 36·4% for Deauville score (DS) 1 (n = 34), 2 (n = 39), 3 (n = 46), 4 (n = 56) and 5 (n = 14) (P < 0·001); and 64·1% and 50·0% for the maximum standardised uptake value (∆SUVmax ) of ≥66% (n = 168) and <66% (n = 21), respectively (P = 0·25). After a median 5·4 years of follow-up, the 5-year PFS was 69·4%, 72·8%, 76·7%, 71·2% and 47·6% by DS 1-5 (P = 0·01); and 72·6% and 57·1% by ∆SUVmax of ≥66% and <66% (P = 0·03), respectively. The association with DS remained in multivariable analyses, and was consistent for OS. Early complete metabolic response (DS 1-3) at interim PET/CT after two cycles of R-CHOP in DLBCL was associated with a higher end-of-treatment complete and overall response rate; however, only DS-5 patients had inferior PFS and OS.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Anciano , Anciano de 80 o más Años , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Fluorodesoxiglucosa F18/análisis , Humanos , Linfoma de Células B Grandes Difuso/epidemiología , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Pronóstico , Estudios Prospectivos , Rituximab/uso terapéutico , Reino Unido/epidemiología , Vincristina/uso terapéutico , Adulto Joven
4.
Neurology ; 95(9): e1244-e1256, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32690786

RESUMEN

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER: NCT00572195. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.


Asunto(s)
Epilepsia Refractaria/terapia , Terapia por Estimulación Eléctrica/métodos , Epilepsias Parciales/terapia , Neuroestimuladores Implantables , Calidad de Vida , Adolescente , Adulto , Anciano , Trastorno Depresivo/epidemiología , Epilepsia Refractaria/fisiopatología , Epilepsia Refractaria/psicología , Epilepsias Parciales/fisiopatología , Epilepsias Parciales/psicología , Femenino , Estudios de Seguimiento , Humanos , Hemorragias Intracraneales/epidemiología , Masculino , Trastornos de la Memoria/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Infecciones Relacionadas con Prótesis/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Estado Epiléptico/epidemiología , Muerte Súbita e Inesperada en la Epilepsia/epidemiología , Suicidio/estadística & datos numéricos , Resultado del Tratamiento , Adulto Joven
5.
Epilepsia ; 61(3): 408-420, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32072621

RESUMEN

OBJECTIVE: To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system. METHODS: We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3 months before MTL resection. RESULTS: We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1 year of follow-up (N = 21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets. SIGNIFICANCE: Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.


Asunto(s)
Lobectomía Temporal Anterior/métodos , Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/cirugía , Lóbulo Temporal/cirugía , Adulto , Anciano , Epilepsia Refractaria/fisiopatología , Terapia por Estimulación Eléctrica , Electrocorticografía , Epilepsia del Lóbulo Temporal/fisiopatología , Femenino , Humanos , Neuroestimuladores Implantables , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio , Procedimientos Neuroquirúrgicos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
7.
J Clin Oncol ; 37(20): 1732-1741, 2019 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-31112475

RESUMEN

PURPOSE: Accurate stratification of patients is an important goal in Hodgkin lymphoma (HL), but the role of pretreatment clinical risk stratification in the context of positron emission tomography (PET) -adapted treatment is unclear. We performed a subsidiary analysis of the RAPID trial to assess the prognostic value of pretreatment risk factors and PET score in determining outcomes. PATIENTS AND METHODS: Patients with stage IA to IIA HL and no mediastinal bulk underwent PET assessment after three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; 143 PET-positive patients (PET score, 3 to 5) received a fourth doxorubicin, bleomycin, vinblastine, and dacarbazine cycle and involved-field radiotherapy, and 419 patients in complete metabolic remission were randomly assigned to receive involved-field radiotherapy (n = 208) or no additional treatment (n = 211). Cox regression was used to investigate the association between PET score and pretreatment risk factors with HL-specific event-free survival (EFS). RESULTS: High PET score was associated with inferior EFS, before (P < .001) and after adjustment (P = .01) for baseline risk stratification. Only patients with a postchemotherapy PET score of 5 (uptake ≥ three times maximum liver uptake) had an increased risk of progression or HL-related death (hazard ratio, 9.4 v score of 3; 95% CI, 2.8 to 31.3 and hazard ratio, 6.7 v score of 4; 95% CI, 1.4 to 31.7). Patients with a PET score of 5 also had inferior progression-free and overall survival. There was no association between European Organisation for Research and Treatment of Cancer or German Hodgkin Study Group risk group and EFS, before or after adjusting for PET score (all P > .4). CONCLUSION: In RAPID, a positive PET scan did not carry uniform prognostic weight; only a PET score of 5 was associated with inferior outcomes. This suggests that in future trials involving patients without B symptoms or mediastinal bulk, a score of 5 rather than a positive PET result should be used to guide treatment escalation in early-stage HL.


Asunto(s)
Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Tomografía de Emisión de Positrones , Medición de Riesgo/métodos , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/administración & dosificación , Terapia Combinada , Dacarbazina/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Radioterapia , Inducción de Remisión , Factores de Riesgo , Resultado del Tratamiento , Reino Unido , Vinblastina/administración & dosificación , Adulto Joven
8.
Epilepsy Behav Case Rep ; 11: 52-53, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30705819

RESUMEN

Mortality associated with cannabis used for treatment of epilepsy is not well documented. We discuss two fatalities in the setting of epilepsy and self-determined therapy with cannabis (SDTC). One patient had probable sudden unexpected death in epilepsy, the second death was due to seizure-associated drowning. Both directed SDTC over conventional anti-seizure medications. Where recreational cannabis is legal, decisions to use cannabis are often self-directed and independent of physician advice of cannabis risks, in part because physicians may not be aware of the risk of SDTC. Further study of morbidity and mortality of SDTC in patients with epilepsy is needed.

9.
Epilepsy Behav Case Rep ; 11: 14-17, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30591882

RESUMEN

OBJECTIVES: To examine outcome of bilateral extracranial to intracranial (EC-IC) bypass surgeries for a Down syndrome patient with hard-to-treat epilepsy and moyamoya. MATERIALS AND METHODS: Superficial temporal arteries were anastamosed using an indirect bypass technique to middle cerebral arteries bilaterally to help limit perfusion deficits and seizure controls. RESULTS: Two superficial temporal to middle cerebral artery indirect bypass surgeries were performed within 3 months. Post-revascularization improvements included seizure control, gait, perfusion, wakefulness, language and quality of life. CONCLUSION: In patients with Down syndrome and moyamoya, improvements in seizure control and quality of life may occur with EC-IC bypass procedures.

10.
Brain Behav ; 8(11): e01126, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30299002

RESUMEN

BACKGROUND: Skateboarders, snowboarders, and surfers all show stance preferences for which foot is forward while moving. We are unaware of other animals than humans with a stance preference, perhaps excepting Osprey, who fly their caught fish beneath them in a foot-forward stance. We hypothesize there should be no difference between left foot forward, right foot back (conventional) versus right foot forward left foot back (goofy) stances or for fish holding with unilateral left or right foot. Online, publicly available, convenience images of Osprey catching fish were accessed and assessed by five independent reviewers using different Internet search engines or online photo series. Stance preference and footedness were tested using chi-square analysis. RESULTS: Stance preferences were evident with the left foot forward (conventional stance) on average 64-78% of the time (all p < 0.02). No difference in foot preference for either one-foot grabs of fish during flight or for non-flight nest/perch fish holding was evident. CONCLUSION: Flight stance of Osprey holding fish shows a lateralized preference in a proportion similar to skateboarders of surfers. We discuss stance preferences in the setting of complex movements and potential flight and survival advantages for Osprey.


Asunto(s)
Falconiformes/fisiología , Pie/fisiología , Lateralidad Funcional/fisiología , Animales , Vuelo Animal/fisiología , Movimiento/fisiología , Postura/fisiología
11.
Epilepsy Behav Case Rep ; 10: 65-70, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30073145

RESUMEN

OBJECTIVES: To investigate if glucose levels influence seizure patterns. MATERIALS AND METHODS: In a patient with RNS/NeuroPace implanted bi-temporally and type 1 diabetes mellitus, seizure event times and onset locations were matched to continuous tissue glucose. RESULTS: Left focal seizure (LFS, n = 22) glucoses averaged 169 mg/dL, while right focal seizure (RFS, n = 23) glucoses averaged 131 mg/dL (p = 0.03). LFS occurred at mean time 17:02 while RFS occurred at 04:23. LFS spread to the contralateral side (n = 19) more than RFS (n = 2). CONCLUSION: Seizure onset laterality and spread vary with glucose and time of seizure.

12.
Epilepsy Behav Case Rep ; 9: 33-36, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29692968

RESUMEN

OBJECTIVES: To match responsive neurostimulator (RNS) and polysomnographic data to determine if RNS detections and stimulations correlate with measurements of sleep disordered breathing and continuous glucose measurements (CGM). MATERIALS AND METHODS: In a patient with an RNS with detection/stimulation leads implanted bi-temporally detection-stimulation counts were matched by time with coinciding polysomnogram and CGM data. RESULTS: Temporal dispersion of RNS DSC were independent of measures of sleep apnea, hypopnea or glucose. CONCLUSION: Hippocampal nighttime responsive neurostimulation therapies did not appear to worsen measures of normal or abnormal sleep.

13.
J Nucl Med ; 58(10): 1666-1671, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28385795

RESUMEN

We report the safety, biodistribution, and internal radiation dosimetry, in humans with thyroid cancer, of 18F-tetrafluoroborate (18F-TFB), a novel PET radioligand for imaging the human sodium/iodide symporter (hNIS). Methods: Serial whole-body PET scans of 5 subjects with recently diagnosed thyroid cancer were acquired before surgery for up to 4 h after injection of 184 ± 15 MBq of 18F-TFB. Activity was determined in whole blood, plasma, and urine. Mean organ-absorbed doses and effective doses were calculated via quantitative image analysis and using OLINDA/EXM software. Results: Images showed a high uptake of 18F-TFB in known areas of high hNIS expression (thyroid, salivary glands, and stomach). Excretion was predominantly renal. No adverse effects in relation to safety of the radiopharmaceutical were observed. The effective dose was 0.0326 ± 0.0018 mSv/MBq. The critical tissues/organs receiving the highest mean sex-averaged absorbed doses were the thyroid (0.135 ± 0.079 mSv/MBq), stomach (0.069 ± 0.022 mSv/MBq), and salivary glands (parotids, 0.031 ± 0.011 mSv/MBq; submandibular, 0.061 ± 0.031 mSv/MBq). Other organs of interest were the bladder (0.102 ± 0.046 mSv/MBq) and kidneys (0.029 ± 0.009 mSv/MBq). Conclusion: Imaging using 18F-TFB imparts a radiation exposure similar in magnitude to many other 18F-labeled radiotracers. 18F-TFB shows a biodistribution similar to 99mTc-pertechnetate, a known nonorganified hNIS tracer, and is pharmacologically and radiobiologically safe in humans. Phase 2 trials for 18F-TFB as an hNIS imaging agent are warranted.


Asunto(s)
Boratos/farmacocinética , Ácidos Bóricos/farmacocinética , Regulación Neoplásica de la Expresión Génica , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Seguridad , Simportadores/metabolismo , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/metabolismo , Boratos/efectos adversos , Boratos/metabolismo , Ácidos Bóricos/efectos adversos , Ácidos Bóricos/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiometría , Distribución Tisular
14.
Epilepsy Behav Case Rep ; 6: 70-2, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27668181

RESUMEN

OBJECTIVES: This study aimed to investigate mirtazapine-induced changes in responsive neurostimulator (RNS) recordings in a patient with epilepsy. MATERIALS AND METHODS: Cortical detection/stimulation counts from an RNS implanted in a patient with bitemporal epilepsy were matched to mirtazapine use to see if that drug altered hippocampal excitability. RESULTS: Mirtazapine decreased hippocampal stability; when mirtazapine was held after a washout period, DSC counts declined, but when it was retrialed, DSC counts increased. Responsive epilepsy neurostimulator system data helped design an optimal and individualized medication regimen for our patient with drug-resistant focal epilepsy. CONCLUSIONS: Responsive neurostimulator systems in epilepsy may assess a medication's effect on hippocampal excitability. Mirtazapine worsened hippocampal excitability in a patient with bitemporal epilepsy.

15.
Epilepsy Behav Case Rep ; 5: 72-4, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27222798

RESUMEN

OBJECTIVES: The objective of this study was to review software errors known as single event upsets (SEUs) or bit flips due to cosmic rays in epilepsy neurostimulators. MATERIALS AND METHODS: A case report of a single event upset or bit flip is discussed; device manufacturers and publicly available data were queried for both incidence and types of error as well as strategies of software error mitigation. RESULTS: Neurostimulators, like other implanted devices such as pacemakers, are prone to single event upsets. Strategies for SEU mitigation are reviewed. CONCLUSIONS: Cosmic radiation can threaten RAM and settings of neurostimulators; neuromodulation teams and device designers need to take this threat into account when designing multifunctional neuromodulation systems.

16.
Blood ; 127(12): 1531-8, 2016 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-26747247

RESUMEN

International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Tomografía de Emisión de Positrones/métodos , Biopsia , Bleomicina/uso terapéutico , Médula Ósea/patología , Dacarbazina/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Fluorodesoxiglucosa F18/análisis , Humanos , Masculino , Estadificación de Neoplasias/métodos , Radiofármacos/análisis , Vinblastina/uso terapéutico
17.
EJNMMI Res ; 5(1): 64, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26576995

RESUMEN

BACKGROUND: Accurate alignment between histopathology slices and positron emission tomography (PET) images is important for radiopharmaceutical validation studies. Limited data is available on the registration accuracy that can be achieved between PET and histopathology slices acquired under routine pathology conditions where slices may be non-parallel, non-contiguously cut and of standard block size. The purpose of this study was to demonstrate a method for aligning PET images and histopathology slices acquired from patients with laryngeal cancer and to assess the registration accuracy obtained under these conditions. METHODS: Six subjects with laryngeal cancer underwent a (64)Cu-copper-II-diacetyl-bis(N4-methylthiosemicarbazone) ((64)Cu-ATSM) PET computed tomography (CT) scan prior to total laryngectomy. Sea urchin spines were inserted into the pathology specimen to act as fiducial markers. The specimen was fixed in formalin, as per standard histopathology operating procedures, and was then CT scanned and cut into millimetre-thick tissue slices. A subset of the tissue slices that included both tumour and fiducial markers was taken and embedded in paraffin blocks. Subsequently, microtome sectioning and haematoxylin and eosin staining were performed to produce 5-µm-thick tissue sections for microscopic digitisation. A series of rigid registration procedures was performed between the different imaging modalities (PET; in vivo CT-i.e. the CT component of the PET-CT; ex vivo CT; histology slices) with the ex vivo CT serving as the reference image. In vivo and ex vivo CTs were registered using landmark-based registration. Histopathology and ex vivo CT images were aligned using the sea urchin spines with additional anatomical landmarks where available. Registration errors were estimated using a leave-one-out strategy for in vivo to ex vivo CT and were estimated from the RMS landmark accuracy for histopathology to ex vivo CT. RESULTS: The mean ± SD accuracy for registration of the in vivo to ex vivo CT images was 2.66 ± 0.66 mm, and the accuracy for registration of histopathology to ex vivo CT was 0.86 ± 0.41 mm. Estimating the PET to in vivo CT registration accuracy to equal the PET-CT alignment accuracy of 1 mm resulted in an overall average registration error between PET and histopathology slices of 3.0 ± 0.7 mm. CONCLUSIONS: We have developed a registration method to align PET images and histopathology slices with an accuracy comparable to the spatial resolution of the PET images.

18.
J Nucl Med ; 56(12): 1855-61, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26383153

RESUMEN

UNLABELLED: Integrins are upregulated on both tumor cells and associated vasculature, where they play an important role in angiogenesis and metastasis. Fluciclatide is an arginine-glycine-aspartic acid peptide with high affinity for αvß3/αvß5 integrin, which can be radiolabeled for PET imaging of angiogenesis. Thus, (18)F-fluciclatide is a potential biomarker of therapeutic response to antiangiogenic inhibitors. The aim of this study was to evaluate the reproducibility of (18)F-fluciclatide in multiple solid-tumor types. METHODS: Thirty-nine patients underwent PET/CT scanning at 40, 65, and 90 min after injection of (18)F-fluciclatide (maximum, 370 MBq) on 2 separate days (2-9 d apart). Patients did not receive any therapy between PET/CT scans. (18)F-fluciclatide images were reported and quantitative measures of uptake were extracted using the PERCIST methodology. Intrasubject reproducibility of PET uptake in all measurable lesions was evaluated by calculating relative differences in SUV between PET scans for each lesion during the 2 imaging sessions. RESULTS: Thirty-nine measurable lesions were detected in 26 patients. Lesion uptake correlated strongly across imaging sessions (r = 0.92, P < 0.05, at 40 min; r = 0.94, P < 0.05, at 65 min; r = 0.94, P < 0.05, at 90 min) with a mean relative difference and SD of the relative difference of 0.006 ± 0.18 at 40 min, 0.003 ± 0.19 at 65 min, and 0.025 ± 0.20 at 90 min. This reflects 95% limits of repeatability of 35%-39% for the difference between the 2 SUV measurements or a variability of 18%-20% in agreement from that observed in well-calibrated multicenter (18)F-FDG studies. CONCLUSION: The test-retest reproducibility of (18)F-fluciclatide across multiple tumor types has been measured and shown to be acceptable. This is an important step in the development of this in vivo biomarker to identify and quantify response to antiangiogenic therapy in cancer patients.


Asunto(s)
Neoplasias/diagnóstico por imagen , Péptidos , Polietilenglicoles , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/uso terapéutico , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Control de Calidad , Reproducibilidad de los Resultados
20.
PLoS One ; 10(5): e0124165, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25938522

RESUMEN

PURPOSE: A number of recent publications have proposed that a family of image-derived indices, called texture features, can predict clinical outcome in patients with cancer. However, the investigation of multiple indices on a single data set can lead to significant inflation of type-I errors. We report a systematic review of the type-I error inflation in such studies and review the evidence regarding associations between patient outcome and texture features derived from positron emission tomography (PET) or computed tomography (CT) images. METHODS: For study identification PubMed and Scopus were searched (1/2000-9/2013) using combinations of the keywords texture, prognostic, predictive and cancer. Studies were divided into three categories according to the sources of the type-I error inflation and the use or not of an independent validation dataset. For each study, the true type-I error probability and the adjusted level of significance were estimated using the optimum cut-off approach correction, and the Benjamini-Hochberg method. To demonstrate explicitly the variable selection bias in these studies, we re-analyzed data from one of the published studies, but using 100 random variables substituted for the original image-derived indices. The significance of the random variables as potential predictors of outcome was examined using the analysis methods used in the identified studies. RESULTS: Fifteen studies were identified. After applying appropriate statistical corrections, an average type-I error probability of 76% (range: 34-99%) was estimated with the majority of published results not reaching statistical significance. Only 3/15 studies used a validation dataset. For the 100 random variables examined, 10% proved to be significant predictors of survival when subjected to ROC and multiple hypothesis testing analysis. CONCLUSIONS: We found insufficient evidence to support a relationship between PET or CT texture features and patient survival. Further fit for purpose validation of these image-derived biomarkers should be supported by appropriate biological and statistical evidence before their association with patient outcome is investigated in prospective studies.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Área Bajo la Curva , Reacciones Falso Positivas , Humanos , Estimación de Kaplan-Meier , Probabilidad , Curva ROC
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